HCBP6 Is Involved in the Development of Hepatic Steatosis Induced by High-Fat Diet and CCL4 in Rats

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A Case Report and a Review of Literature" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "519" "paginaFinal" => "524" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 5604 "Ancho" => 4416 "Tamanyo" => 1133597 ] ] "descripcion" => array:1 [ "en" => "CT, MRI and cholangiography images. A. CT (contrast enhanced, transversal scan) and B. MRI (T2-weighted, transversal scan) -Cystoid multilocular formation in left hepatic lobe S4 (red arrow), with a dilation of the left intrahepatic bile ducts (blue arrow), in close proximity to the stomach (green arrow). C,D. MRI (T2-weighted, coronal scan) showing the same multilocular formation in left hepatic lobe S4 (red arrows), with a dilation of the left intrahepatic bile ducts (blue arrow) and intraluminal tumor masses (white arrow). E. Percutaneous transhepatic cholangiography and drainage - dilation of the left intrahepatic bile ducts (blue arrows), with irregular stenosis centrally and narrow common bile duct (yellow arrows); contrast is also visible in the cystoid formation (red arrows) and the gallbladder (orange arrow)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Lumir Kunovsky, Zdenek Kala, Roman Svaton, Petr Moravcik, Jan Mazanec, Jakub Husty, Vladimir Prochazka" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Lumir" "apellidos" => "Kunovsky" ] 1 => array:2 [ "nombre" => "Zdenek" "apellidos" => "Kala" ] 2 => array:2 [ "nombre" => "Roman" "apellidos" => "Svaton" ] 3 => array:2 [ "nombre" => "Petr" "apellidos" => "Moravcik" ] 4 => array:2 [ "nombre" => "Jan" "apellidos" => "Mazanec" ] 5 => array:2 [ "nombre" => "Jakub" "apellidos" => "Husty" ] 6 => array:2 [ "nombre" => "Vladimir" "apellidos" => "Prochazka" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S166526811930208X?idApp=UINPBA00004N" "url" => "/16652681/0000001700000003/v1_201905160920/S166526811930208X/v1_201905160920/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119302066" "issn" => "16652681" "doi" => "10.5604/01.3001.0011.7395" "estado" => "S300" "fechaPublicacion" => "2018-05-01" "aid" => "70063" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2018;17:501-10" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 272 "formatos" => array:3 [ "EPUB" => 18 "HTML" => 178 "PDF" => 76 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Therapeutic Effect of HGF on NASH Mice Through HGF/c-Met and JAK2-STAT3 Signalling Pathway" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "501" "paginaFinal" => "510" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2280 "Ancho" => 4442 "Tamanyo" => 1622685 ] ] "descripcion" => array:1 [ "en" => "Liver H&E staining (200x) after treatment. More severe steatohepatitis was observed in HFD mice when HGF, c-Met, or JAK2 was inhibited. A. Control group. B-F. Different intervention groups as shown in figure. * P < 0.05, ** P < 0.01, *** P < 0.001 vs. group A (control);† P < 0.05, †† P < 0.01, ††† P < 0.001 vs. group B (HFD + normal saline); § P < 0.05, §§ P < 0.01, §§§ P < 0.001 vs. group C (HFD + HGF)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ning Li, Zhangfeng Dou, Jinchun Liu, Bao Chai, Yue Li, Xiuqin An, Peiling Chu, Xiaolan Zhang" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Ning" "apellidos" => "Li" ] 1 => array:2 [ "nombre" => "Zhangfeng" "apellidos" => "Dou" ] 2 => array:2 [ "nombre" => "Jinchun" "apellidos" => "Liu" ] 3 => array:2 [ "nombre" => "Bao" "apellidos" => "Chai" ] 4 => array:2 [ "nombre" => "Yue" "apellidos" => "Li" ] 5 => array:2 [ "nombre" => "Xiuqin" "apellidos" => "An" ] 6 => array:2 [ "nombre" => "Peiling" "apellidos" => "Chu" ] 7 => array:2 [ "nombre" => "Xiaolan" "apellidos" => "Zhang" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119302066?idApp=UINPBA00004N" "url" => "/16652681/0000001700000003/v1_201905160920/S1665268119302066/v1_201905160920/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "titulo" => "HCBP6 Is Involved in the Development of Hepatic Steatosis Induced by High-Fat Diet and CCL4 in Rats" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "511" "paginaFinal" => "518" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Yong-Ping Zheng, Xian-Yang Zhong, Yu-Shu Huang, Can-Bin Zheng" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Yong-Ping" "apellidos" => "Zheng" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Xian-Yang" "apellidos" => "Zhong" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Yu-Shu" "apellidos" => "Huang" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] ] ] 3 => array:4 [ "nombre" => "Can-Bin" "apellidos" => "Zheng" "email" => array:1 [ 0 => "canbinzheng2@yahoo.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "**" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Gastroenterology, Shantou Central Hospital, Affiliated Hospital of Sun Yat-Sen University, Shantou, Guangdong province, China" "etiqueta" => "*" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Endocrine and Metabolic Diseases, 1st Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong province, China" "etiqueta" => "**" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "*" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1671 "Ancho" => 4371 "Tamanyo" => 654534 ] ] "descripcion" => array:1 [ "en" => "Weight and pathological change of livers from rats induced by high-fat diet and carbon tetrachloride (CCL4). A. Percentage of liver-to-body weight was shown in this panel. The percentage of liver-to-body weight from control group was significantly lower than that from Group 1 and Group 2 (*P < 0.05 compared with Group 1;† P < 0.05 compared with Group 2; n = 6). B. Pathological observation of hepatic steatosis induced by high-fat diet and CCL4. Liver sections from control group, Group 1, and Group 2 were stained with H&E and Oil Red O. Original magnification: 200." ] ] ] "textoCompleto" => "IntroductionHepatic steatosis is characterized by lipid dysregulation and fat accumulation in the liver. It is a major complication of obesity, hyperlipidemia, insulin resistance (IR), and non-alcoholic fatty liver disease (NAFLD).<a class="elsevierStyleCrossRef" href="#bib0005">1</a> If untreated, benign steatosis can gradually advance to steatohepatitis, fibrosis, cirrhosis, and even liver cancer.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>,<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Many risk factors can promote hepatic steatosis through different mechanisms, such as metabolic diseases, alcohol, virus, drugs, and nutritional disorders, with IR being the most common feature leading to hepatic lipid accumulation.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Multiple lines of evidence have demonstrated that various genes, including sterol regulatory element binding protein 1c (SREBP-lc), FoxOl, AKT2, and PPARγ, are involved in IR-induced hepatic steatosis.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>Hepatitis C virus core-binding protein 6 (HCBP6) was originally identified as a hepatitis C virus (HCV) corebinding protein.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> HCV core protein has been shown to play an important role in hepatic steatosis.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Researches have proved that HCBP6 mRNA and protein levels exhibited time- and dose-dependent increases in a cellular model of lipid-overload hepatic steatosis in vitro and HCBP6 was found as a negative regulator and sensor of intracellular TG levels.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Still, the biological function of HCBP6 in hepatic steatosis is not fully understood. Whether HCBP6 is involved in the development of hepatic steatosis in vivo is yet to be investigated.SREBP-1c belongs to the basic helix-loop-helix-leucine zipper family of transcription factors and plays a key role in regulating fatty acid synthesis and TG accumulation in the liver.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> HCV core protein induces TG accumulation by stimulating SREBP-lc gene expression and HCBP6 binds the HCV core protein.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Whether HCBP6 is involved in SREBP1c-FASN-mediated TG accumulation has yet to be determined. Here, we demonstrate that HCBP6 is involved in the development of hepatic steatosis induced by high-fat diet and carbon tetrachloride (CCL4) in rats and HCBP6 is negatively related to SREBP-1c. The results offer new insights into the pathophysiology of hepatic steatosis.Material and MethodsAnimals and treatment schedulesWistar rats, weighing 190-210 g, were provided by laboratory center, Shantou University Medical College. A standard laboratory diet and water were available ad libitum. The animal room was maintained humidity with a 12h (7:00 a.m. -7:00 p.m.) light/dark cycle. After 1 week on the basal diet, 18 animals were randomly allocated into 3 groups: Group 1, Group 2, and control group. Each group contained 6 rats. Rats in model groups received a high-fat diet and subcutaneous injection of 30% CCL4 in liquid paraffin oil (0.2 mL/100 g body weight) twice a week for 3 weeks (Group 1) and 5 weeks (Group 2) respectively. Rats in the control group received subcutaneous injection of normal saline and normal food feed instead. After 3 weeks (Group 1) or 5 weeks (Group 2 and control group), rats were fasted overnight and sacrificed. The serum was separated for further investigation. Rat livers were weighed and frozen or fixed in 10% formalin. All experiment protocols were approved by ethics committee of Shantou Central Hospital. All animals received humane care according to the criteria outlined in the “Guide for the Care and Use of Laboratory Animals” prepared by the National Academy of Sciences and published by the National Institutes of Health (NIH publication 86-23 revised 1985).Evaluation of liver pathologyA histological study was performed following a midline laparotomy to remove the left lateral lobe of rat liver. Livers were harvested at the end of the experiment. Weighed, immediately placed in 10% buffered formalin, and embedded in paraffin. Liver sections were stained with hematoxylin and eosin (H&E) using standard technique. To further confirm lipid droplet accumulation, frozen liver sections were stained with Oil Red O. Investigators were blinded to the group identity of each section, and biopsies were classified into four categories depending on fat accumulation using a previously established method as follows: Grade 0, no fat observed in the liver; Grade 1, < 33% of hepatocytes contained fat vacuoles; Grade 2, 33-66% of hepatocytes contained fat vacuoles; Grade 3, > 66% of hepatocytes contained fat vacuoles.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>Biochemical determinationsAfter being treated for 3 weeks (Group 1) or 5 weeks (Group 2 and control group), rats were fasted overnight and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglycerides (TGs) were measured with an automatic biochemical analyzer.Evaluations of TC and TGs in liver tissuesExactly 3 ml of ethanol - acetone (1:1) was added to the liver tissues (200 mg), which were then homogenized in an ice bath and mixed thoroughly at 4°C overnight. After 24 h, the liver tissues were centrifuged at 3000 rpm and 4 °C for 20 min. Subsequently, the supernatant was transferred to a new tube, then TC and TGs were measured based on the instructions on TC and TG assay kit (Jiancheng Institute of Bio Engineering, Nanjing, China) using a colorimetric method.Immunofluorescence and confocal imagingSpecimens of liver tissues were cut into 4-μιτι sections using a cryotome (Leica CM 3000; Leica, München, Germany) and fixed in acetone for 10 min. To quench the endogenous peroxidase activity, sections were treated with 0.3% H2O2 for 10 min. Then they were treated with normal non-immune goat serum for 15 min at room temperature to block nonspecific sites. The sections were incubated with goat anti-rat HCBP6 polyclonal antibody (1:100, Santa Cruz Biotechnology, USA) and rabbit antirat SREBP-1c polyclonal antibody (1:250, Santa Cruz Biotechnology, USA) at 4°C overnight, washed with tris-buffered saline (TBS 0.1 M, pH 7.4) and incubated with Alexa-Fluor-594-labelled donkey anti-goat IgG and FITC-labelled goat anti-rabbit IgG (ZSGB-BIO, Beijing, China) at 37°C for 1.5 h. After washed with TBS, The nuclei were stained by DAPI (Abcam, Cambridge, UK) for 10 min at room temperature. Confocal images were collected by the slit scanning laser confocal microscope (LSM710, Carl Zeiss, Germany) and image software (Zen 2011, Carl Zeiss MicroImaging GHBH, Germany). To compare the intensity of immunofluorescence, the average percentage of positive immunostaining cells to 10 random confocal images was measureed for the labeled index protein HCBP6 and SREBP-1c.RNA analysisTotal RNA was extracted using TRIzol® Reagent (Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s protocol. 1.0 μg of total RNA was used as a template for first strand cDNA synthesis using PrimerScript® RT Master Mix kit (TaKaRa, Tokyo, Japan). Real-time PCR was performed using SYBR® Premix Ex TaqTM kit (TaKaRa, Tokyo, Japan) on LightCycler 480 Realtime PCR System (Roche, USA). The sequences of primers used in this study were as follows (forward and reverse): HCBP6, 5'-CTT TTC GGG CAT GAG AGT CG-3' and 5'-GAA TCG TCA GCT GCT CCT TG -3'; SREBPlc, 5'-CAC TTC CAG CTA GAC CCC AA-3' and 5'-GGT GAG AGC CTT GAG ACA GT-3'; GAPDH, 5'-GTT ACC AGG GCT GCC TTC TC-3' and 5'- GAT GGT GAT GGG TTT CCC GT-3'.Western blotting analysisThe samples for Western blots analysis were liver lysates, which were incubated in RIPA lysis buffer: 50 mM Tris, 150 mM NaCl, 1% Triton X-100, 1% sodium deoxycholate, 0.1% SDS, 2 mM EDTA, and protease inhibitors (pH 7.4). Protein content of the samples was measured by BCA Protein Assay Kit (Thermo, Rockford, IL, USA). Proteins (40 μg per sample) were separated by SDS-PAGE with 12% polyacrylamide gels and transferred onto PVDF membranes. The blots were blocked with a solution of 5% (wt / vol) skim milk in TBS containing 0.1% Tween-20 for 1 h at room temperature and incubated overnight at 4°C with primary goat anti-rat HCBP6 antibody (1:800, Santa Cruz, Santa Cruz, CA, USA), rabbit anti-rat SREBP-1c antibody (1:1000, Santa cruz, Santa Cruz, CA, USA), and rabbit anti-rat β-actin antibody (1:2000, Cell Signaling Technology, Danvers, MA, USA). After rinsed in TBS (pH 7.8) containing 0.1% Tween-20, the blots were incubated with horseradish peroxidase-conjugated antibody (1:2000, Cell Signaling Technology, Danvers, MA, USA) for 1 h. HCBP6, SREBP-1c, and β-actin proteins were detected by enhanced chemiluminescence system. The integrated intensity for the protein bands was determined by scanning densitometry and analyzed by Glyko BandScan 5.0. The data were analyzed using relative intensity to the constitutive marker, β-actin.Statistical analysisDifferences among groups were examined by one-way ANOVA followed by Tukey-Kramer multiple comparison tests. Values are expressed as the mean ± standard deviation. A value of P < 0.05 was considered statistically significant.ResultsCharacteristics of animalsA total of 18 rats were investigated in the study. The initial body weights of the male and female rats were similar (200 ± 10 g). At the end of the intervention, there was a significant difference in the percentage of liver-to-body weight between control group and model groups, Group 1 (4.56% ± 0.56%), Group 2 (4.63% ± 0.30%) vs. control group (3.12% ± 0.23%), P < 0.05 (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>A).<elsevierMultimedia ident="f0005"></elsevierMultimedia>Hepatic architectureAs H&E staining showed, histological analysis of the hepatic fragments in the control group exhibited well-preserved architecture with characteristic hepatocytes distributed homogenously throughout the hepatic parenchyma. Group 1 and Group 2 exhibited significant alterations, including tissue disorganization with macroand micro-vesicular steatosis in the cytoplasm of the hepatocytes, as well as the presence of multiple foci of inflammable infiltrates, being prominent in rats of Group 2 (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>B). Quantifying the fatty infiltration by a previously published scoring system, the mean fatty infiltration in the treated Group 1 and Group 2 were both Grade 2 while the control group was quantified as Grade 0. Oil-Red-O stain displayed abundant accumulation of fat droplets in hepatocytes from rats of Group 1 and Group 2 (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>B). These liver histology results suggested that hepatic steatosis was successfully induced in model groups.Biochemical determinations and liver TG contentThe serum levels of ALT, AST, TC, and TGs in the control group were 53.00 ± 15.06 U/L, 90.75 ± 24.00 U/L, 1.42 ± 0.36 mmol/L, and 0.82 ± 0.94 mmol/L. While the serum levels of ALT, AST, TC, and TGs were 101.25 ± 19.00 U/L, 137.00 ± 35.79 U/L, 2.45 ± 0.35 mmol/L, and 1.09 ± 0.12 mmol/L in Group 1 and 127.00 ± 20.45 U/L, 147.25 ± 27.40 U/L, 2.03 ± 0.20 mmol/L, and 1.03 ± 0.12 mmol/L in Group 2. The Group 1 and Group 2 rats showed significant serum elevations of ALT, AST, TC, and TGs compared to the control group. In liver tissues, the levels of TC and TGs were 1.06 ± 0.18 mg/g and 1.75 ± 0.31 mg/g in the control group, 2.58 ± 0.21 mg/g and 4.35 ± 0.39 in Group 1, and 2.93 ± 0.32 mg/g and 4.41 ± 0.62 mg/g in Group 2 respectively. Similarly, liver TC and TGs elevated remarkably in model groups compared with the control group (n = 6, P < 0.05); (<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>).<elsevierMultimedia ident="t0005"></elsevierMultimedia>Immunofluorescence evaluation of HCBP6 and SREBP-1cImmunofluorescence staining was performed to detect the HCBP6 and SREBP-1c expression in the liver tissues of rats separated from Group 1, Group 2, and control group (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>A). The percentages of HCBP6 positive cells for Group 1, Group 2, and control group were 5.22% ± 1.74%, 6.93% ± 1.04%, and 43.85% ± 5.89%, respectively. While the percentages of SREBP-1c positive cells for Group 1, Group 2, and control group were 72.15% ± 8.24%, 83.61% ± 8.52%, and 8.84% ± 0.91%, respectively. It was significantly lower for HCBP6 expression and higher for SREBP-1c expression in hepatocytes of Group 1 and Group 2 rats, compared with control rats (n = 6, P < 0.05) (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>B). But there was no significant difference between Group 1 and Group 2 rats.<elsevierMultimedia ident="f0010"></elsevierMultimedia>mRNA expressions of HCBP6 and SREBP-1cThe mRNA expressions of HCBP6 and SREBP-1c in hepatocytes of Group 1, Group 2, and control rats were shown in <a class="elsevierStyleCrossRef" href="#t0010">table 2</a> and <a class="elsevierStyleCrossRef" href="#f0010">figure 2</a>C. Compared with control rats, the mRNA expression of HCBP6 was significantly lower in hepatocytes of Group 1 and Group 2 rats (n = 6, P < 0.05). Conversely, a significantly higher expression of SREBP-1c was detected in hepatocytes of Group 1 and Group 2 rats than that in hepatocytes of control rats (n = 6, P < 0.05).<elsevierMultimedia ident="t0010"></elsevierMultimedia>Protein expressions of HCBP6 and SREBP-1cProtein expressions of the HCBP6 and SREBP-1c were analyzed through western blotting on the liver samples. Compared with control rats, the protein expression of HCBP6 was decreased in hepatocytes of Group 1 and Group 2 rats. While SREBP-1c protein expression of hepatocytes in both Group 1 and Group 2 rats was significantly higher than that in control rats (n = 6, P < 0.05) (<a class="elsevierStyleCrossRef" href="#f0010">Figures 2</a>D and 2E, and <a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>).DiscussionNAFLD is an increasing prevalent health problem that ranges from simple fatty infiltration of the liver parenchyma (non-alcoholic simple fatty liver, NAFL) to steatosis with inflammation and hepatocellular ballooning (non-alcoholic steatohepatitis, NASH) and ultimately cirrhosi.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> It is estimated that 1 billion people currently suffer from some form of NAFLD.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> Liver steatosis, marked as the first stage of NAFLD, is closely associated with obesity, type 2 diabetes mellitus, IR, and drug-induced liver injury.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Steatosis is considered as a benign reversible event, while NASH has a potential to lead to cirrhosis and hepatocellular carcinoma. As much as 10-25% of liver steatosis patients progress to NASH and 2-3% of NASH patients develop into liver cancer.<a class="elsevierStyleCrossRef" href="#bib0075">15</a>,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Hence, liver steatosis is of major concern for worldwide health.Pathologically, hepatic steatosis is featured by the accumulation of fat in at least 5% of hepatocytes. Hepatic steatosis occurs when the production and removal of intrahepatic TGs become unbalanced due to reduced fatty acid oxidation as well as increased de novo lipogenesis. Maintaining TG homeostasis is essential for normal liver function.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Many risk factors can promote hepatic steatosis through different mechanisms, such as metabolic diseases, alcohol, virus, drugs, and nutritional disorders, with IR being the most common feature leading to hepatic lipid accumulation.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Various genes, including SREBP-1c, LXR, AKT2, and FASN, have been demonstrated to be involved in IR-induced hepatic steatosis.<a class="elsevierStyleCrossRefs" href="#bib0095">19</a>–<a class="elsevierStyleCrossRef" href="#bib0110">22</a>It has classically been found that HCV, especially genotype 3, exerts direct metabolic effects which leads to liver steatosis.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> HCV core protein plays an important role in the development of hepatic steatosis in HCV infection.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Researches have demonstrated that HCV core is localized on the endoplasmic reticulum and on lipid droplets which suggests a relationship between the expression of the HCV core protein and cellular lipid metabolism.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> HCBP6 has been identified as a HCV core-binding protein and shown to inhibit HCV core protein transactivation ef- fects.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>,<a class="elsevierStyleCrossRef" href="#bib0120">24</a> It has also been found to regulate the transcriptional activity of the alpha chain of nascent polypeptide-associated complex promoter and the expression of genes involved in cell proliferation, signal transduction, growth, and differentiation.<a class="elsevierStyleCrossRef" href="#bib0125">25</a>,<a class="elsevierStyleCrossRef" href="#bib0130">26</a> Studies have revealed that HCBP6 is a negative regulator and sensor of intracellular TG levels in vitro and HCPB6 expression is induced by TGs in a time- and dose-dependent manner.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>SREBP-1c belongs to the basic helix-loop-helix-leucine zipper family of transcription factors and plays a key role in regulating fatty acid synthesis and TG accumulation in the liver.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Three mammalian SREBP isoforms (SREBP-1a, SREBP-1c, and SREBP-2) are encoded by two genes, SREBF1 and SREBF2, and have distinct but overlapping functions in lipogenic gene regulation. Previous studies have reported that SREBP-1a activates fatty acid and cholesterol synthesis. SREBP-1c activates fatty acid and TG synthesis, and SREBP-2 activates cholesterol synthesis and uptake.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> SREBP-1c increases the transcriptional activity of genes involved in hepatic fatty acid synthesis (including FASN, ACC, and SCD), enhances transcription of genes required for fatty acid synthesis, and predominates in the liver.<a class="elsevierStyleCrossRef" href="#bib0140">28</a>,<a class="elsevierStyleCrossRef" href="#bib0145">29</a> Alterations to the SREBP-1c-FASN pathway can result in liver steatosis and type 2 diabetes.<a class="elsevierStyleCrossRef" href="#bib0150">30</a>Various animal models of NAFLD have been developed involving genetic and diet manipulation, treatment with toxins as well as combination models.<a class="elsevierStyleCrossRef" href="#bib0155">31</a> In our study, we established the model of liver steatosis by a high-fat diet and CCL4 subcutaneous injection. This method accords with the pattern of NAFLD development in some degree and has been extensively studied.<a class="elsevierStyleCrossRefs" href="#bib0160">32</a>–<a class="elsevierStyleCrossRef" href="#bib0175">35</a> The pathology and liver function study revealed that hepatic steatosis was successfully induced in model groups. To further explore whether HCBP6 was involved with a time-dependent manner, we designed model groups treated for 3 weeks and 5 weeks. Two groups both exhibited fatty infiltration of quantifying Grade 2 while Group 2 represented more serious steatohepatitis.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> However, we did not include the investigation on the change of HCBP6 within clear stages of NAFLD to NASH, even to fibrosis, which was worth our further investigation.Previous studies have demonstrated that HCV core protein induced TG accumulation by stimulating SREBP-1c gene expression and HCBP6 negatively regulated intracellular TG levels in hepatoma cell lines via the SREBP-1c/ FASN Pathway in vitro.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>,<a class="elsevierStyleCrossRef" href="#bib0050">10</a> The results implied that HCBP6 may impact TG metabolism through the regulation of SREBP-1c in vivo. In the current study, we investigated the in vivo change and revealed HCBP6 expression was downregulated in hepatic steatosis in rats, consistent with in vitro observations by Gao, et al.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Our experimental results showed the expression of HCBP6 was significantly decreased in livers of rats induced by high-fat diet and CCL4. It continued to maintain at a lower level as treating time prolonged. All above showed HCBP6 was associated with the development of hepatic steatosis in rats. Besides, as a crucial transcription factor in hepatic fatty acid synthesis, SREBP-1c expression was up-regulated in the model groups, negatively correlated with HCBP6. So we speculated that the lower expression of HCBP6 may cause the higher expression of SREBP-1c and activate the SREBP-1c signal pathway, resulting in the increase of fatty acid and TG synthesis and the dysfunction of lipid metabolism in the development of hepatic steatosis. This study offered new insights into the pathophysiology of hepatic steatosis. On the other hand, it also suggested that HCBP6 may be used as a sensitive indicator for NAFLD occurrence and development. It may be an efficient way to prevent and treat NAFLD by promoting the expression of HCBP6.In conclusion, we demonstrate that HCBP6 is involved in the development of hepatic steatosis induced by highfat diet and CCL4 in rats and HCBP6 is negatively related to SREBP-1c. The results offer new insights into the pathophysiology of hepatic steatosis. Thus, our results suggest that HCBP6 may represent a new potential therapeutic target in lipid metabolism and fatty liver management.Abbreviations<ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="u0005">•ALT: alanine aminotransferase.</li><li class="elsevierStyleListItem" id="u0010">•AST: aspartate aminotransferase.</li><li class="elsevierStyleListItem" id="u0015">•CCL4: carbon tetrachloride.</li><li class="elsevierStyleListItem" id="u0020">•H&E: hematoxylin and eosin.</li><li class="elsevierStyleListItem" id="u0025">•HCBP6: hepatitis C virus core-binding protein 6.</li><li class="elsevierStyleListItem" id="u0030">•HCV: hepatitis C virus.</li><li class="elsevierStyleListItem" id="u0035">•IR: insulin resistance.</li><li class="elsevierStyleListItem" id="u0040">•NAFL: non-alcoholic simple fatty liver.</li><li class="elsevierStyleListItem" id="u0045">•NAFLD: non-alcoholic fatty liver disease.</li><li class="elsevierStyleListItem" id="u0050">•NASH: non-alcoholic steatohepatitis.</li><li class="elsevierStyleListItem" id="u0055">•SREBP-lc: sterol regulatory element binding protein 1c.</li><li class="elsevierStyleListItem" id="u0060">•TBS: tris-buffered saline.</li><li class="elsevierStyleListItem" id="u0065">•TC: total cholesterol.</li><li class="elsevierStyleListItem" id="u0070">•TG: triglyceride.</li></ul>AcknowledgementsThere is no conflict of interest to be declared. This study was supported by Science Foundation of Guangdong province for traditional Chinese medicine research (No. 20131053)." "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1190776" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0010" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1110053" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "s0010" "titulo" => "Material and Methods" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Animals and treatment schedules" ] 1 => array:2 [ "identificador" => "s0020" "titulo" => "Evaluation of liver pathology" ] 2 => array:2 [ "identificador" => "s0025" "titulo" => "Biochemical determinations" ] 3 => array:2 [ "identificador" => "s0030" "titulo" => "Evaluations of TC and TGs in liver tissues" ] 4 => array:2 [ "identificador" => "s0035" "titulo" => "Immunofluorescence and confocal imaging" ] 5 => array:2 [ "identificador" => "s0040" "titulo" => "RNA analysis" ] 6 => array:2 [ "identificador" => "s0045" "titulo" => "Western blotting analysis" ] 7 => array:2 [ "identificador" => "s0050" "titulo" => "Statistical analysis" ] ] ] 4 => array:3 [ "identificador" => "s0055" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "s0060" "titulo" => "Characteristics of animals" ] 1 => array:2 [ "identificador" => "s0065" "titulo" => "Hepatic architecture" ] 2 => array:2 [ "identificador" => "s0070" "titulo" => "Biochemical determinations and liver TG content" ] 3 => array:2 [ "identificador" => "s0075" "titulo" => "Immunofluorescence evaluation of HCBP6 and SREBP-1c" ] 4 => array:2 [ "identificador" => "s0080" "titulo" => "mRNA expressions of HCBP6 and SREBP-1c" ] 5 => array:2 [ "identificador" => "s0085" "titulo" => "Protein expressions of HCBP6 and SREBP-1c" ] ] ] 5 => array:2 [ "identificador" => "s0090" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "s0095" "titulo" => "Abbreviations" ] 7 => array:2 [ "identificador" => "s0100" "titulo" => "Acknowledgements" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-07-16" "fechaAceptado" => "2017-09-12" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1110053" "palabras" => array:3 [ 0 => "Non-alcoholic fatty liver disease" 1 => "Hepatitis C virus core-binding protein" 2 => "SREBP-1c" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Introduction and alm. Hepatitis C virus core-binding protein 6 (HCBP6) was previously found to be an hepatitis C virus corebinding protein, its biological function remains unclear. Our research aims to investigate the role of HCBP6 in the development of hepatic steatosis induced by high-fat diet and carbon tetrachloride (CCL4) in rats.Material and methods. Eighteen Wistar rats were randomly allocated into 3 groups: control group, model group 1, and model group 2. The control group was treated with a standard diet for 5 weeks. Model groups were treated with high-fat diet and CCL4 injection twice a week for 3 weeks in Group 1 and 5 weeks in Group 2, respectively. After the intervention, hepatic steatosis was observed by histological staining with hematoxylin and eosin (H&E) and Oil Red O staining. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglycerides (TGs) were measured. The TG content in liver homogenates was evaluated. Expressions of HCBP6 and SREBP-1c were determined by immunofluorescence, quantitative real-time PCR, and Western blot analysis.Results. Hepatic steatosis was successfully induced in model groups. ALT, AST, TC, and TGs elevated in model groups compared with those in control group (P < 0.05). Hepatic steatosis induced by high-fat diet and CCL4 resulted in low expression of HCBP6 and high expression of SREBP-1c in the liver of rats (P < 0.05).Conclusion. HCBP6 is involved in the development of high-fat diet- and CCL4-induced hepatic steatosis and related negatively with SREBP-1c." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1671 "Ancho" => 4371 "Tamanyo" => 654534 ] ] "descripcion" => array:1 [ "en" => "Weight and pathological change of livers from rats induced by high-fat diet and carbon tetrachloride (CCL4). A. Percentage of liver-to-body weight was shown in this panel. The percentage of liver-to-body weight from control group was significantly lower than that from Group 1 and Group 2 (*P < 0.05 compared with Group 1;† P < 0.05 compared with Group 2; n = 6). B. Pathological observation of hepatic steatosis induced by high-fat diet and CCL4. Liver sections from control group, Group 1, and Group 2 were stained with H&E and Oil Red O. Original magnification: 200." ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 4980 "Ancho" => 4408 "Tamanyo" => 1776665 ] ] "descripcion" => array:1 [ "en" => "Expressions of HCBP6 and SREBP-1c in hepatocytes of Group 1, Group 2, and control rats. A. Immunofluorescence staining of HCBP6 and SREBP-1c in hepatocytes (Origina magnification: 100). Magnified images are shown in the bottom right of each section. B. Comparisons of percentages of HCBP6 + and SREBP-1c + hepatocytes (*P < 0.05 compared for HCBP6 with control;† P < 0.05 compared for SREBP-1c with control; n = 6). C. Comparisons of HCBP6 and SREBP-1c mRNA expressions in hepatocytes (*P < 0.05 compared for HCBP6 with control;† P < 0.05 compared for SREBP-1c with control; n = 6). D. Protein expressions of HCBP6 and SRBP-1c in hepatocytes detected by Western blot analysis. E. Comparisons of integrated intensity for HCBP6 and SREBP-1c (*P < 0.05 compared for HCBP6 with control;† P < 0.05 compared for SREBP-1c with control; n = 6)." ] ] 2 => array:7 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "ALT: alanine aminotransferase. AST: aspartate aminotransferase. TC: total cholesterol. TG: triglycerides;" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ALT (U/L) (serum) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AST (U/L) (serum) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TC (mmol/L) (serum) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TG (mmol/L) (serum) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TC (mg/g) (liver tissue) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TG (mg/g) (liver tissue) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53.00±15.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.75 ± 24.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.42±0.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.82 ± 0.94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.06±0.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.75 ± 0.31 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">101.25± 19.00<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">137.00 ± 35.79<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.45± 0.35<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.09 ± 0.12<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.58± 0.21<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.35 ± 0.39<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">127.00± 20.45<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">147.25 ± 27.40<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.03± 0.20<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.03 ± 0.12<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.93± 0.32<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.41 ± 0.62<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2031879.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "P < 0.05 comparing with control group." ] ] ] "descripcion" => array:1 [ "en" => "ALT, AST, TC, and TG levels in serum and TC and TG levels in liver tissues." ] ] 3 => array:7 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Gene \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">mRNA level<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Protein level <a class="elsevierStyleCrossRef" href="#tblfn0015">b</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HCBP6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.69 ± 0.08 <a class="elsevierStyleCrossRef" href="#tblfn0020">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.274 ± 0.034 <a class="elsevierStyleCrossRef" href="#tblfn0020">c</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.63 ± 0.10 <a class="elsevierStyleCrossRef" href="#tblfn0020">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.217 ± 0.033 <a class="elsevierStyleCrossRef" href="#tblfn0020">c</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.11 ± 0.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.540 ± 0.061 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SREBP-lc \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.08 ± 0.79 <a class="elsevierStyleCrossRef" href="#tblfn0020">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.837 ± 0.090 <a class="elsevierStyleCrossRef" href="#tblfn0020">c</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.32 ± 0.74 <a class="elsevierStyleCrossRef" href="#tblfn0020">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.907 ± 0.062 <a class="elsevierStyleCrossRef" href="#tblfn0020">c</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.16 ± 0.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.318 ± 0.037 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2031880.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "mRNA abundance was analyzed using the 2-ΔΔCt Ct method with GAPDH as the constitutive marker." ] 1 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "b" "nota" => "The protein expression was analyzed 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Yong-Ping Zheng*,*, Xian-Yang Zhong*, Yu-Shu Huang*, Can-Bin Zheng**

* Department of Gastroenterology, Shantou Central Hospital, Affiliated Hospital of Sun Yat-Sen University, Shantou, Guangdong province, China

** Department of Endocrine and Metabolic Diseases, 1st Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong province, China

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            "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">CT&#44; MRI and cholangiography images&#46; <span class="elsevierStyleBold">A&#46;</span> CT &#40;contrast enhanced&#44; transversal scan&#41; and <span class="elsevierStyleBold">B&#46;</span> MRI &#40;T2-weighted&#44; transversal scan&#41; -Cystoid multilocular formation in left hepatic lobe S4 &#40;red arrow&#41;&#44; with a dilation of the left intrahepatic bile ducts &#40;blue arrow&#41;&#44; in close proximity to the stomach &#40;green arrow&#41;&#46; <span class="elsevierStyleBold">C&#44;D&#46;</span> MRI &#40;T2-weighted&#44; coronal scan&#41; showing the same multilocular formation in left hepatic lobe S4 &#40;red arrows&#41;&#44; with a dilation of the left intrahepatic bile ducts &#40;blue arrow&#41; and intraluminal tumor masses &#40;white arrow&#41;&#46; <span class="elsevierStyleBold">E&#46;</span> Percutaneous transhepatic cholangiography and drainage - dilation of the left intrahepatic bile ducts &#40;blue arrows&#41;&#44; with irregular stenosis centrally and narrow common bile duct &#40;yellow arrows&#41;&#59; contrast is also visible in the cystoid formation &#40;red arrows&#41; and the gallbladder &#40;orange arrow&#41;&#46;</p>"
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          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Weight and pathological change of livers from rats induced by high-fat diet and carbon tetrachloride &#40;CCL4&#41;&#46; <span class="elsevierStyleBold">A&#46;</span> Percentage of liver-to-body weight was shown in this panel&#46; The percentage of liver-to-body weight from control group was significantly lower than that from Group 1 and Group 2 &#40;&#42;P &#60; 0&#46;05 compared with Group 1&#59;<span class="elsevierStyleSup">&#8224;</span> P &#60; 0&#46;05 compared with Group 2&#59; n &#61; 6&#41;&#46; <span class="elsevierStyleBold">B&#46;</span> Pathological observation of hepatic steatosis induced by high-fat diet and CCL4&#46; Liver sections from control group&#44; Group 1&#44; and Group 2 were stained with H&#38;E and Oil Red O&#46; Original magnification&#58; 200&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Hepatic steatosis is characterized by lipid dysregulation and fat accumulation in the liver&#46; It is a major complication of obesity&#44; hyperlipidemia&#44; insulin resistance &#40;IR&#41;&#44; and non-alcoholic fatty liver disease &#40;NAFLD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> If untreated&#44; benign steatosis can gradually advance to steatohepatitis&#44; fibrosis&#44; cirrhosis&#44; and even liver cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Many risk factors can promote hepatic steatosis through different mechanisms&#44; such as metabolic diseases&#44; alcohol&#44; virus&#44; drugs&#44; and nutritional disorders&#44; with IR being the most common feature leading to hepatic lipid accumulation&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Multiple lines of evidence have demonstrated that various genes&#44; including sterol regulatory element binding protein 1c &#40;SREBP-lc&#41;&#44; FoxOl&#44; AKT2&#44; and PPAR&#947;&#44; are involved in IR-induced hepatic steatosis&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Hepatitis C virus core-binding protein 6 &#40;HCBP6&#41; was originally identified as a hepatitis C virus &#40;HCV&#41; corebinding protein&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> HCV core protein has been shown to play an important role in hepatic steatosis&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Researches have proved that HCBP6 mRNA and protein levels exhibited time- and dose-dependent increases in a cellular model of lipid-overload hepatic steatosis <span class="elsevierStyleItalic">in vitro</span> and HCBP6 was found as a negative regulator and sensor of intracellular TG levels&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Still&#44; the biological function of HCBP6 in hepatic steatosis is not fully understood&#46; Whether HCBP6 is involved in the development of hepatic steatosis <span class="elsevierStyleItalic">in vivo</span> is yet to be investigated&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">SREBP-1c belongs to the basic helix-loop-helix-leucine zipper family of transcription factors and plays a key role in regulating fatty acid synthesis and TG accumulation in the liver&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> HCV core protein induces TG accumulation by stimulating SREBP-lc gene expression and HCBP6 binds the HCV core protein&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Whether HCBP6 is involved in SREBP1c-FASN-mediated TG accumulation has yet to be determined&#46; Here&#44; we demonstrate that HCBP6 is involved in the development of hepatic steatosis induced by high-fat diet and carbon tetrachloride &#40;CCL4&#41; in rats and HCBP6 is negatively related to SREBP-1c&#46; The results offer new insights into the pathophysiology of hepatic steatosis&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Material and Methods</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Animals and treatment schedules</span><p id="p0020" class="elsevierStylePara elsevierViewall">Wistar rats&#44; weighing 190-210 g&#44; were provided by laboratory center&#44; Shantou University Medical College&#46; A standard laboratory diet and water were available ad libitum&#46; The animal room was maintained humidity with a 12h &#40;7&#58;00 a&#46;m&#46; -7&#58;00 p&#46;m&#46;&#41; light&#47;dark cycle&#46; After 1 week on the basal diet&#44; 18 animals were randomly allocated into 3 groups&#58; Group 1&#44; Group 2&#44; and control group&#46; Each group contained 6 rats&#46; Rats in model groups received a high-fat diet and subcutaneous injection of 30&#37; CCL4 in liquid paraffin oil &#40;0&#46;2 mL&#47;100 g body weight&#41; twice a week for 3 weeks &#40;Group 1&#41; and 5 weeks &#40;Group 2&#41; respectively&#46; Rats in the control group received subcutaneous injection of normal saline and normal food feed instead&#46; After 3 weeks &#40;Group 1&#41; or 5 weeks &#40;Group 2 and control group&#41;&#44; rats were fasted overnight and sacrificed&#46; The serum was separated for further investigation&#46; Rat livers were weighed and frozen or fixed in 10&#37; formalin&#46; All experiment protocols were approved by ethics committee of Shantou Central Hospital&#46; All animals received humane care according to the criteria outlined in the &#8220;Guide for the Care and Use of Laboratory Animals&#8221; prepared by the National Academy of Sciences and published by the National Institutes of Health &#40;NIH publication 86-23 revised 1985&#41;&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Evaluation of liver pathology</span><p id="p0025" class="elsevierStylePara elsevierViewall">A histological study was performed following a midline laparotomy to remove the left lateral lobe of rat liver&#46; Livers were harvested at the end of the experiment&#46; Weighed&#44; immediately placed in 10&#37; buffered formalin&#44; and embedded in paraffin&#46; Liver sections were stained with hematoxylin and eosin &#40;H&#38;E&#41; using standard technique&#46; To further confirm lipid droplet accumulation&#44; frozen liver sections were stained with Oil Red O&#46; Investigators were blinded to the group identity of each section&#44; and biopsies were classified into four categories depending on fat accumulation using a previously established method as follows&#58; Grade 0&#44; no fat observed in the liver&#59; Grade 1&#44; &#60; 33&#37; of hepatocytes contained fat vacuoles&#59; Grade 2&#44; 33-66&#37; of hepatocytes contained fat vacuoles&#59; Grade 3&#44; &#62; 66&#37; of hepatocytes contained fat vacuoles&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Biochemical determinations</span><p id="p0030" class="elsevierStylePara elsevierViewall">After being treated for 3 weeks &#40;Group 1&#41; or 5 weeks &#40;Group 2 and control group&#41;&#44; rats were fasted overnight and serum levels of alanine aminotransferase &#40;ALT&#41;&#44; aspartate aminotransferase &#40;AST&#41;&#44; total cholesterol &#40;TC&#41;&#44; and triglycerides &#40;TGs&#41; were measured with an automatic biochemical analyzer&#46;</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Evaluations of TC and TGs in liver tissues</span><p id="p0035" class="elsevierStylePara elsevierViewall">Exactly 3 ml of ethanol - acetone &#40;1&#58;1&#41; was added to the liver tissues &#40;200 mg&#41;&#44; which were then homogenized in an ice bath and mixed thoroughly at 4&#176;C overnight&#46; After 24 h&#44; the liver tissues were centrifuged at 3000 rpm and 4 &#176;C for 20 min&#46; Subsequently&#44; the supernatant was transferred to a new tube&#44; then TC and TGs were measured based on the instructions on TC and TG assay kit &#40;Jiancheng Institute of Bio Engineering&#44; Nanjing&#44; China&#41; using a colorimetric method&#46;</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Immunofluorescence and confocal imaging</span><p id="p0040" class="elsevierStylePara elsevierViewall">Specimens of liver tissues were cut into 4-&#956;&#953;&#964;&#953; sections using a cryotome &#40;Leica CM 3000&#59; Leica&#44; M&#252;nchen&#44; Germany&#41; and fixed in acetone for 10 min&#46; To quench the endogenous peroxidase activity&#44; sections were treated with 0&#46;3&#37; H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span> for 10 min&#46; Then they were treated with normal non-immune goat serum for 15 min at room temperature to block nonspecific sites&#46; The sections were incubated with goat anti-rat HCBP6 polyclonal antibody &#40;1&#58;100&#44; Santa Cruz Biotechnology&#44; USA&#41; and rabbit antirat SREBP-1c polyclonal antibody &#40;1&#58;250&#44; Santa Cruz Biotechnology&#44; USA&#41; at 4&#176;C overnight&#44; washed with tris-buffered saline &#40;TBS 0&#46;1 M&#44; pH 7&#46;4&#41; and incubated with Alexa-Fluor-594-labelled donkey anti-goat IgG and FITC-labelled goat anti-rabbit IgG &#40;ZSGB-BIO&#44; Beijing&#44; China&#41; at 37&#176;C for 1&#46;5 h&#46; After washed with TBS&#44; The nuclei were stained by DAPI &#40;Abcam&#44; Cambridge&#44; UK&#41; for 10 min at room temperature&#46; Confocal images were collected by the slit scanning laser confocal microscope &#40;LSM710&#44; Carl Zeiss&#44; Germany&#41; and image software &#40;Zen 2011&#44; Carl Zeiss MicroImaging GHBH&#44; Germany&#41;&#46; To compare the intensity of immunofluorescence&#44; the average percentage of positive immunostaining cells to 10 random confocal images was measureed for the labeled index protein HCBP6 and SREBP-1c&#46;</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">RNA analysis</span><p id="p0045" class="elsevierStylePara elsevierViewall">Total RNA was extracted using TRIzol<span class="elsevierStyleSup">&#174;</span> Reagent &#40;Invitrogen&#44; Carlsbad&#44; CA&#44; USA&#41; according to the manufacturer&#8217;s protocol&#46; 1&#46;0 &#956;g of total RNA was used as a template for first strand cDNA synthesis using PrimerScript<span class="elsevierStyleSup">&#174;</span> RT Master Mix kit &#40;TaKaRa&#44; Tokyo&#44; Japan&#41;&#46; Real-time PCR was performed using SYBR<span class="elsevierStyleSup">&#174;</span> Premix Ex TaqTM kit &#40;TaKaRa&#44; Tokyo&#44; Japan&#41; on LightCycler 480 Realtime PCR System &#40;Roche&#44; USA&#41;&#46; The sequences of primers used in this study were as follows &#40;forward and reverse&#41;&#58; HCBP6&#44; 5&#39;-CTT TTC GGG CAT GAG AGT CG-3&#39; and 5&#39;-GAA TCG TCA GCT GCT CCT TG -3&#39;&#59; SREBPlc&#44; 5&#39;-CAC TTC CAG CTA GAC CCC AA-3&#39; and 5&#39;-GGT GAG AGC CTT GAG ACA GT-3&#39;&#59; GAPDH&#44; 5&#39;-GTT ACC AGG GCT GCC TTC TC-3&#39; and 5&#39;- GAT GGT GAT GGG TTT CCC GT-3&#39;&#46;</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Western blotting analysis</span><p id="p0050" class="elsevierStylePara elsevierViewall">The samples for Western blots analysis were liver lysates&#44; which were incubated in RIPA lysis buffer&#58; 50 mM Tris&#44; 150 mM NaCl&#44; 1&#37; Triton X-100&#44; 1&#37; sodium deoxycholate&#44; 0&#46;1&#37; SDS&#44; 2 mM EDTA&#44; and protease inhibitors &#40;pH 7&#46;4&#41;&#46; Protein content of the samples was measured by BCA Protein Assay Kit &#40;Thermo&#44; Rockford&#44; IL&#44; USA&#41;&#46; Proteins &#40;40 &#956;g per sample&#41; were separated by SDS-PAGE with 12&#37; polyacrylamide gels and transferred onto PVDF membranes&#46; The blots were blocked with a solution of 5&#37; &#40;wt &#47; vol&#41; skim milk in TBS containing 0&#46;1&#37; Tween-20 for 1 h at room temperature and incubated overnight at 4&#176;C with primary goat anti-rat HCBP6 antibody &#40;1&#58;800&#44; Santa Cruz&#44; Santa Cruz&#44; CA&#44; USA&#41;&#44; rabbit anti-rat SREBP-1c antibody &#40;1&#58;1000&#44; Santa cruz&#44; Santa Cruz&#44; CA&#44; USA&#41;&#44; and rabbit anti-rat &#946;-actin antibody &#40;1&#58;2000&#44; Cell Signaling Technology&#44; Danvers&#44; MA&#44; USA&#41;&#46; After rinsed in TBS &#40;pH 7&#46;8&#41; containing 0&#46;1&#37; Tween-20&#44; the blots were incubated with horseradish peroxidase-conjugated antibody &#40;1&#58;2000&#44; Cell Signaling Technology&#44; Danvers&#44; MA&#44; USA&#41; for 1 h&#46; HCBP6&#44; SREBP-1c&#44; and &#946;-actin proteins were detected by enhanced chemiluminescence system&#46; The integrated intensity for the protein bands was determined by scanning densitometry and analyzed by Glyko BandScan 5&#46;0&#46; The data were analyzed using relative intensity to the constitutive marker&#44; &#946;-actin&#46;</p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Statistical analysis</span><p id="p0055" class="elsevierStylePara elsevierViewall">Differences among groups were examined by one-way ANOVA followed by Tukey-Kramer multiple comparison tests&#46; Values are expressed as the mean &#177; standard deviation&#46; A value of P &#60; 0&#46;05 was considered statistically significant&#46;</p></span></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Results</span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Characteristics of animals</span><p id="p0060" class="elsevierStylePara elsevierViewall">A total of 18 rats were investigated in the study&#46; The initial body weights of the male and female rats were similar &#40;200 &#177; 10 g&#41;&#46; At the end of the intervention&#44; there was a significant difference in the percentage of liver-to-body weight between control group and model groups&#44; Group 1 &#40;4&#46;56&#37; &#177; 0&#46;56&#37;&#41;&#44; Group 2 &#40;4&#46;63&#37; &#177; 0&#46;30&#37;&#41; <span class="elsevierStyleItalic">vs&#46;</span> control group &#40;3&#46;12&#37; &#177; 0&#46;23&#37;&#41;&#44; P &#60; 0&#46;05 &#40;<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>A&#41;&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia></span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Hepatic architecture</span><p id="p0065" class="elsevierStylePara elsevierViewall">As H&#38;E staining showed&#44; histological analysis of the hepatic fragments in the control group exhibited well-preserved architecture with characteristic hepatocytes distributed homogenously throughout the hepatic parenchyma&#46; Group 1 and Group 2 exhibited significant alterations&#44; including tissue disorganization with macroand micro-vesicular steatosis in the cytoplasm of the hepatocytes&#44; as well as the presence of multiple foci of inflammable infiltrates&#44; being prominent in rats of Group 2 &#40;<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>B&#41;&#46; Quantifying the fatty infiltration by a previously published scoring system&#44; the mean fatty infiltration in the treated Group 1 and Group 2 were both Grade 2 while the control group was quantified as Grade 0&#46; Oil-Red-O stain displayed abundant accumulation of fat droplets in hepatocytes from rats of Group 1 and Group 2 &#40;<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>B&#41;&#46; These liver histology results suggested that hepatic steatosis was successfully induced in model groups&#46;</p></span><span id="s0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Biochemical determinations and liver TG content</span><p id="p0070" class="elsevierStylePara elsevierViewall">The serum levels of ALT&#44; AST&#44; TC&#44; and TGs in the control group were 53&#46;00 &#177; 15&#46;06 U&#47;L&#44; 90&#46;75 &#177; 24&#46;00 U&#47;L&#44; 1&#46;42 &#177; 0&#46;36 mmol&#47;L&#44; and 0&#46;82 &#177; 0&#46;94 mmol&#47;L&#46; While the serum levels of ALT&#44; AST&#44; TC&#44; and TGs were 101&#46;25 &#177; 19&#46;00 U&#47;L&#44; 137&#46;00 &#177; 35&#46;79 U&#47;L&#44; 2&#46;45 &#177; 0&#46;35 mmol&#47;L&#44; and 1&#46;09 &#177; 0&#46;12 mmol&#47;L in Group 1 and 127&#46;00 &#177; 20&#46;45 U&#47;L&#44; 147&#46;25 &#177; 27&#46;40 U&#47;L&#44; 2&#46;03 &#177; 0&#46;20 mmol&#47;L&#44; and 1&#46;03 &#177; 0&#46;12 mmol&#47;L in Group 2&#46; The Group 1 and Group 2 rats showed significant serum elevations of ALT&#44; AST&#44; TC&#44; and TGs compared to the control group&#46; In liver tissues&#44; the levels of TC and TGs were 1&#46;06 &#177; 0&#46;18 mg&#47;g and 1&#46;75 &#177; 0&#46;31 mg&#47;g in the control group&#44; 2&#46;58 &#177; 0&#46;21 mg&#47;g and 4&#46;35 &#177; 0&#46;39 in Group 1&#44; and 2&#46;93 &#177; 0&#46;32 mg&#47;g and 4&#46;41 &#177; 0&#46;62 mg&#47;g in Group 2 respectively&#46; Similarly&#44; liver TC and TGs elevated remarkably in model groups compared with the control group &#40;n &#61; 6&#44; P &#60; 0&#46;05&#41;&#59; &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia></span><span id="s0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Immunofluorescence evaluation of HCBP6 and SREBP-1c</span><p id="p0075" class="elsevierStylePara elsevierViewall">Immunofluorescence staining was performed to detect the HCBP6 and SREBP-1c expression in the liver tissues of rats separated from Group 1&#44; Group 2&#44; and control group &#40;<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>A&#41;&#46; The percentages of HCBP6 positive cells for Group 1&#44; Group 2&#44; and control group were 5&#46;22&#37; &#177; 1&#46;74&#37;&#44; 6&#46;93&#37; &#177; 1&#46;04&#37;&#44; and 43&#46;85&#37; &#177; 5&#46;89&#37;&#44; respectively&#46; While the percentages of SREBP-1c positive cells for Group 1&#44; Group 2&#44; and control group were 72&#46;15&#37; &#177; 8&#46;24&#37;&#44; 83&#46;61&#37; &#177; 8&#46;52&#37;&#44; and 8&#46;84&#37; &#177; 0&#46;91&#37;&#44; respectively&#46; It was significantly lower for HCBP6 expression and higher for SREBP-1c expression in hepatocytes of Group 1 and Group 2 rats&#44; compared with control rats &#40;n &#61; 6&#44; P &#60; 0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>B&#41;&#46; But there was no significant difference between Group 1 and Group 2 rats&#46;</p><elsevierMultimedia ident="f0010"></elsevierMultimedia></span><span id="s0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">mRNA expressions of HCBP6 and SREBP-1c</span><p id="p0080" class="elsevierStylePara elsevierViewall">The mRNA expressions of HCBP6 and SREBP-1c in hepatocytes of Group 1&#44; Group 2&#44; and control rats were shown in <a class="elsevierStyleCrossRef" href="#t0010">table 2</a> and <a class="elsevierStyleCrossRef" href="#f0010">figure 2</a>C&#46; Compared with control rats&#44; the mRNA expression of HCBP6 was significantly lower in hepatocytes of Group 1 and Group 2 rats &#40;n &#61; 6&#44; P &#60; 0&#46;05&#41;&#46; Conversely&#44; a significantly higher expression of SREBP-1c was detected in hepatocytes of Group 1 and Group 2 rats than that in hepatocytes of control rats &#40;n &#61; 6&#44; P &#60; 0&#46;05&#41;&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia></span><span id="s0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Protein expressions of HCBP6 and SREBP-1c</span><p id="p0085" class="elsevierStylePara elsevierViewall">Protein expressions of the HCBP6 and SREBP-1c were analyzed through western blotting on the liver samples&#46; Compared with control rats&#44; the protein expression of HCBP6 was decreased in hepatocytes of Group 1 and Group 2 rats&#46; While SREBP-1c protein expression of hepatocytes in both Group 1 and Group 2 rats was significantly higher than that in control rats &#40;n &#61; 6&#44; P &#60; 0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#f0010">Figures 2</a>D and 2E&#44; and <a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#41;&#46;</p></span></span><span id="s0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Discussion</span><p id="p0090" class="elsevierStylePara elsevierViewall">NAFLD is an increasing prevalent health problem that ranges from simple fatty infiltration of the liver parenchyma &#40;non-alcoholic simple fatty liver&#44; NAFL&#41; to steatosis with inflammation and hepatocellular ballooning &#40;non-alcoholic steatohepatitis&#44; NASH&#41; and ultimately cirrhosi&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> It is estimated that 1 billion people currently suffer from some form of NAFLD&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Liver steatosis&#44; marked as the first stage of NAFLD&#44; is closely associated with obesity&#44; type 2 diabetes mellitus&#44; IR&#44; and drug-induced liver injury&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Steatosis is considered as a benign reversible event&#44; while NASH has a potential to lead to cirrhosis and hepatocellular carcinoma&#46; As much as 10-25&#37; of liver steatosis patients progress to NASH and 2-3&#37; of NASH patients develop into liver cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Hence&#44; liver steatosis is of major concern for worldwide health&#46;</p><p id="p0095" class="elsevierStylePara elsevierViewall">Pathologically&#44; hepatic steatosis is featured by the accumulation of fat in at least 5&#37; of hepatocytes&#46; Hepatic steatosis occurs when the production and removal of intrahepatic TGs become unbalanced due to reduced fatty acid oxidation as well as increased de novo lipogenesis&#46; Maintaining TG homeostasis is essential for normal liver function&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Many risk factors can promote hepatic steatosis through different mechanisms&#44; such as metabolic diseases&#44; alcohol&#44; virus&#44; drugs&#44; and nutritional disorders&#44; with IR being the most common feature leading to hepatic lipid accumulation&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Various genes&#44; including SREBP-1c&#44; LXR&#44; AKT2&#44; and FASN&#44; have been demonstrated to be involved in IR-induced hepatic steatosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">&#8211;</span><a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="p0100" class="elsevierStylePara elsevierViewall">It has classically been found that HCV&#44; especially genotype 3&#44; exerts direct metabolic effects which leads to liver steatosis&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> HCV core protein plays an important role in the development of hepatic steatosis in HCV infection&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Researches have demonstrated that HCV core is localized on the endoplasmic reticulum and on lipid droplets which suggests a relationship between the expression of the HCV core protein and cellular lipid metabolism&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> HCBP6 has been identified as a HCV core-binding protein and shown to inhibit HCV core protein transactivation ef- fects&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> It has also been found to regulate the transcriptional activity of the alpha chain of nascent polypeptide-associated complex promoter and the expression of genes involved in cell proliferation&#44; signal transduction&#44; growth&#44; and differentiation&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Studies have revealed that HCBP6 is a negative regulator and sensor of intracellular TG levels in vitro and HCPB6 expression is induced by TGs in a time- and dose-dependent manner&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="p0105" class="elsevierStylePara elsevierViewall">SREBP-1c belongs to the basic helix-loop-helix-leucine zipper family of transcription factors and plays a key role in regulating fatty acid synthesis and TG accumulation in the liver&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Three mammalian SREBP isoforms &#40;SREBP-1a&#44; SREBP-1c&#44; and SREBP-2&#41; are encoded by two genes&#44; SREBF1 and SREBF2&#44; and have distinct but overlapping functions in lipogenic gene regulation&#46; Previous studies have reported that SREBP-1a activates fatty acid and cholesterol synthesis&#46; SREBP-1c activates fatty acid and TG synthesis&#44; and SREBP-2 activates cholesterol synthesis and uptake&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> SREBP-1c increases the transcriptional activity of genes involved in hepatic fatty acid synthesis &#40;including FASN&#44; ACC&#44; and SCD&#41;&#44; enhances transcription of genes required for fatty acid synthesis&#44; and predominates in the liver&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Alterations to the SREBP-1c-FASN pathway can result in liver steatosis and type 2 diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="p0110" class="elsevierStylePara elsevierViewall">Various animal models of NAFLD have been developed involving genetic and diet manipulation&#44; treatment with toxins as well as combination models&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> In our study&#44; we established the model of liver steatosis by a high-fat diet and CCL4 subcutaneous injection&#46; This method accords with the pattern of NAFLD development in some degree and has been extensively studied&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32</span></a><span class="elsevierStyleSup">&#8211;</span><a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> The pathology and liver function study revealed that hepatic steatosis was successfully induced in model groups&#46; To further explore whether HCBP6 was involved with a time-dependent manner&#44; we designed model groups treated for 3 weeks and 5 weeks&#46; Two groups both exhibited fatty infiltration of quantifying Grade 2 while Group 2 represented more serious steatohepatitis&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> However&#44; we did not include the investigation on the change of HCBP6 within clear stages of NAFLD to NASH&#44; even to fibrosis&#44; which was worth our further investigation&#46;</p><p id="p0115" class="elsevierStylePara elsevierViewall">Previous studies have demonstrated that HCV core protein induced TG accumulation by stimulating SREBP-1c gene expression and HCBP6 negatively regulated intracellular TG levels in hepatoma cell lines via the SREBP-1c&#47; FASN Pathway in vitro&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The results implied that HCBP6 may impact TG metabolism through the regulation of SREBP-1c <span class="elsevierStyleItalic">in vivo&#46;</span> In the current study&#44; we investigated the <span class="elsevierStyleItalic">in vivo</span> change and revealed HCBP6 expression was downregulated in hepatic steatosis in rats&#44; consistent with <span class="elsevierStyleItalic">in vitro</span> observations by Gao&#44; <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Our experimental results showed the expression of HCBP6 was significantly decreased in livers of rats induced by high-fat diet and CCL4&#46; It continued to maintain at a lower level as treating time prolonged&#46; All above showed HCBP6 was associated with the development of hepatic steatosis in rats&#46; Besides&#44; as a crucial transcription factor in hepatic fatty acid synthesis&#44; SREBP-1c expression was up-regulated in the model groups&#44; negatively correlated with HCBP6&#46; So we speculated that the lower expression of HCBP6 may cause the higher expression of SREBP-1c and activate the SREBP-1c signal pathway&#44; resulting in the increase of fatty acid and TG synthesis and the dysfunction of lipid metabolism in the development of hepatic steatosis&#46; This study offered new insights into the pathophysiology of hepatic steatosis&#46; On the other hand&#44; it also suggested that HCBP6 may be used as a sensitive indicator for NAFLD occurrence and development&#46; It may be an efficient way to prevent and treat NAFLD by promoting the expression of HCBP6&#46;</p><p id="p0120" class="elsevierStylePara elsevierViewall">In conclusion&#44; we demonstrate that HCBP6 is involved in the development of hepatic steatosis induced by highfat diet and CCL4 in rats and HCBP6 is negatively related to SREBP-1c&#46; The results offer new insights into the pathophysiology of hepatic steatosis&#46; Thus&#44; our results suggest that HCBP6 may represent a new potential therapeutic target in lipid metabolism and fatty liver management&#46;</p></span><span id="s0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">Abbreviations</span><p id="p0125" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="u0005"><span class="elsevierStyleLabel">&#8226;</span><p id="p0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ALT&#58;</span> alanine aminotransferase&#46;</p></li><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">&#8226;</span><p id="p0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">AST&#58;</span> aspartate aminotransferase&#46;</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">&#8226;</span><p id="p0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">CCL4&#58;</span> carbon tetrachloride&#46;</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">&#8226;</span><p id="p0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">H&#38;E&#58;</span> hematoxylin and eosin&#46;</p></li><li class="elsevierStyleListItem" id="u0025"><span class="elsevierStyleLabel">&#8226;</span><p id="p0150" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HCBP6&#58;</span> hepatitis C virus core-binding protein 6&#46;</p></li><li class="elsevierStyleListItem" id="u0030"><span class="elsevierStyleLabel">&#8226;</span><p id="p0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HCV&#58;</span> hepatitis C virus&#46;</p></li><li class="elsevierStyleListItem" id="u0035"><span class="elsevierStyleLabel">&#8226;</span><p id="p0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">IR&#58;</span> insulin resistance&#46;</p></li><li class="elsevierStyleListItem" id="u0040"><span class="elsevierStyleLabel">&#8226;</span><p id="p0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">NAFL&#58;</span> non-alcoholic simple fatty liver&#46;</p></li><li class="elsevierStyleListItem" id="u0045"><span class="elsevierStyleLabel">&#8226;</span><p id="p0170" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">NAFLD&#58;</span> non-alcoholic fatty liver disease&#46;</p></li><li class="elsevierStyleListItem" id="u0050"><span class="elsevierStyleLabel">&#8226;</span><p id="p0175" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">NASH&#58;</span> non-alcoholic steatohepatitis&#46;</p></li><li class="elsevierStyleListItem" id="u0055"><span class="elsevierStyleLabel">&#8226;</span><p id="p0180" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">SREBP-lc&#58;</span> sterol regulatory element binding protein 1c&#46;</p></li><li class="elsevierStyleListItem" id="u0060"><span class="elsevierStyleLabel">&#8226;</span><p id="p0185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">TBS&#58;</span> tris-buffered saline&#46;</p></li><li class="elsevierStyleListItem" id="u0065"><span class="elsevierStyleLabel">&#8226;</span><p id="p0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">TC&#58;</span> total cholesterol&#46;</p></li><li class="elsevierStyleListItem" id="u0070"><span class="elsevierStyleLabel">&#8226;</span><p id="p0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">TG&#58;</span> triglyceride&#46;</p></li></ul></p></span><span id="s0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0110">Acknowledgements</span><p id="p0200" class="elsevierStylePara elsevierViewall">There is no conflict of interest to be declared&#46; This study was supported by Science Foundation of Guangdong province for traditional Chinese medicine research &#40;No&#46; 20131053&#41;&#46;</p></span></span>"
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              "identificador" => "abs0010"
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        1 => array:2 [
          "identificador" => "xpalclavsec1110053"
          "titulo" => "Keywords"
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        2 => array:2 [
          "identificador" => "s0005"
          "titulo" => "Introduction"
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        3 => array:3 [
          "identificador" => "s0010"
          "titulo" => "Material and Methods"
          "secciones" => array:8 [
            0 => array:2 [
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              "titulo" => "Animals and treatment schedules"
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              "titulo" => "Evaluation of liver pathology"
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            2 => array:2 [
              "identificador" => "s0025"
              "titulo" => "Biochemical determinations"
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            3 => array:2 [
              "identificador" => "s0030"
              "titulo" => "Evaluations of TC and TGs in liver tissues"
            ]
            4 => array:2 [
              "identificador" => "s0035"
              "titulo" => "Immunofluorescence and confocal imaging"
            ]
            5 => array:2 [
              "identificador" => "s0040"
              "titulo" => "RNA analysis"
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            6 => array:2 [
              "identificador" => "s0045"
              "titulo" => "Western blotting analysis"
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              "titulo" => "Statistical analysis"
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          "titulo" => "Results"
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              "identificador" => "s0060"
              "titulo" => "Characteristics of animals"
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            1 => array:2 [
              "identificador" => "s0065"
              "titulo" => "Hepatic architecture"
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            2 => array:2 [
              "identificador" => "s0070"
              "titulo" => "Biochemical determinations and liver TG content"
            ]
            3 => array:2 [
              "identificador" => "s0075"
              "titulo" => "Immunofluorescence evaluation of HCBP6 and SREBP-1c"
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            4 => array:2 [
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              "titulo" => "mRNA expressions of HCBP6 and SREBP-1c"
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              "identificador" => "s0085"
              "titulo" => "Protein expressions of HCBP6 and SREBP-1c"
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          "titulo" => "Discussion"
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          "titulo" => "Abbreviations"
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          "titulo" => "Acknowledgements"
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          "titulo" => "References"
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    "fechaRecibido" => "2017-07-16"
    "fechaAceptado" => "2017-09-12"
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          "titulo" => "Keywords"
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          "palabras" => array:3 [
            0 => "Non-alcoholic fatty liver disease"
            1 => "Hepatitis C virus core-binding protein"
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Introduction and alm&#46;</span> Hepatitis C virus core-binding protein 6 &#40;HCBP6&#41; was previously found to be an hepatitis C virus corebinding protein&#44; its biological function remains unclear&#46; Our research aims to investigate the role of HCBP6 in the development of hepatic steatosis induced by high-fat diet and carbon tetrachloride &#40;CCL4&#41; in rats&#46;</p><p id="sp0225" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Material and methods&#46;</span> Eighteen Wistar rats were randomly allocated into 3 groups&#58; control group&#44; model group 1&#44; and model group 2&#46; The control group was treated with a standard diet for 5 weeks&#46; Model groups were treated with high-fat diet and CCL4 injection twice a week for 3 weeks in Group 1 and 5 weeks in Group 2&#44; respectively&#46; After the intervention&#44; hepatic steatosis was observed by histological staining with hematoxylin and eosin &#40;H&#38;E&#41; and Oil Red O staining&#46; Serum levels of alanine aminotransferase &#40;ALT&#41;&#44; aspartate aminotransferase &#40;AST&#41;&#44; total cholesterol &#40;TC&#41;&#44; and triglycerides &#40;TGs&#41; were measured&#46; The TG content in liver homogenates was evaluated&#46; Expressions of HCBP6 and SREBP-1c were determined by immunofluorescence&#44; quantitative real-time PCR&#44; and Western blot analysis&#46;</p><p id="sp0325" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Results&#46;</span> Hepatic steatosis was successfully induced in model groups&#46; ALT&#44; AST&#44; TC&#44; and TGs elevated in model groups compared with those in control group &#40;P &#60; 0&#46;05&#41;&#46; Hepatic steatosis induced by high-fat diet and CCL4 resulted in low expression of HCBP6 and high expression of SREBP-1c in the liver of rats &#40;P &#60; 0&#46;05&#41;&#46;</p><p id="sp0425" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Conclusion&#46;</span> HCBP6 is involved in the development of high-fat diet- and CCL4-induced hepatic steatosis and related negatively with SREBP-1c&#46;</p></span>"
      ]
    ]
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      0 => array:7 [
        "identificador" => "f0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Weight and pathological change of livers from rats induced by high-fat diet and carbon tetrachloride &#40;CCL4&#41;&#46; <span class="elsevierStyleBold">A&#46;</span> Percentage of liver-to-body weight was shown in this panel&#46; The percentage of liver-to-body weight from control group was significantly lower than that from Group 1 and Group 2 &#40;&#42;P &#60; 0&#46;05 compared with Group 1&#59;<span class="elsevierStyleSup">&#8224;</span> P &#60; 0&#46;05 compared with Group 2&#59; n &#61; 6&#41;&#46; <span class="elsevierStyleBold">B&#46;</span> Pathological observation of hepatic steatosis induced by high-fat diet and CCL4&#46; Liver sections from control group&#44; Group 1&#44; and Group 2 were stained with H&#38;E and Oil Red O&#46; Original magnification&#58; 200&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "f0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 4980
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        "descripcion" => array:1 [
          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Expressions of HCBP6 and SREBP-1c in hepatocytes of Group 1&#44; Group 2&#44; and control rats&#46; <span class="elsevierStyleBold">A&#46;</span> Immunofluorescence staining of HCBP6 and SREBP-1c in hepatocytes &#40;Origina magnification&#58; 100&#41;&#46; Magnified images are shown in the bottom right of each section&#46; <span class="elsevierStyleBold">B&#46;</span> Comparisons of percentages of HCBP6 <span class="elsevierStyleSup">&#43;</span> and SREBP-1c <span class="elsevierStyleSup">&#43;</span> hepatocytes &#40;&#42;P &#60; 0&#46;05 compared for HCBP6 with control&#59;<span class="elsevierStyleSup">&#8224;</span> P &#60; 0&#46;05 compared for SREBP-1c with control&#59; n &#61; 6&#41;&#46; <span class="elsevierStyleBold">C&#46;</span> Comparisons of HCBP6 and SREBP-1c mRNA expressions in hepatocytes &#40;&#42;P &#60; 0&#46;05 compared for HCBP6 with control&#59;<span class="elsevierStyleSup">&#8224;</span> P &#60; 0&#46;05 compared for SREBP-1c with control&#59; n &#61; 6&#41;&#46; D&#46; Protein expressions of HCBP6 and SRBP-1c in hepatocytes detected by Western blot analysis&#46; <span class="elsevierStyleBold">E&#46;</span> Comparisons of integrated intensity for HCBP6 and SREBP-1c &#40;&#42;P &#60; 0&#46;05 compared for HCBP6 with control&#59;<span class="elsevierStyleSup">&#8224;</span> P &#60; 0&#46;05 compared for SREBP-1c with control&#59; n &#61; 6&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="np0005" class="elsevierStyleSimplePara elsevierViewall">ALT&#58; alanine aminotransferase&#46; AST&#58; aspartate aminotransferase&#46; TC&#58; total cholesterol&#46; TG&#58; triglycerides&#59;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ALT &#40;U&#47;L&#41; &#40;serum&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AST &#40;U&#47;L&#41; &#40;serum&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TC &#40;mmol&#47;L&#41; &#40;serum&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TG &#40;mmol&#47;L&#41; &#40;serum&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TC &#40;mg&#47;g&#41; &#40;liver tissue&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TG &#40;mg&#47;g&#41; &#40;liver tissue&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#46;00&#177;15&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&#46;75 &#177; 24&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;42&#177;0&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;82 &#177; 0&#46;94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;06&#177;0&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;75 &#177; 0&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Group 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">101&#46;25&#177; 19&#46;00<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">137&#46;00 &#177; 35&#46;79<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;45&#177; 0&#46;35<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;09 &#177; 0&#46;12<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;58&#177; 0&#46;21<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;35 &#177; 0&#46;39<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Group 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">127&#46;00&#177; 20&#46;45<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">147&#46;25 &#177; 27&#46;40<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;03&#177; 0&#46;20<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;03 &#177; 0&#46;12<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;93&#177; 0&#46;32<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;41 &#177; 0&#46;62<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005"><span class="elsevierStyleItalic">P &#60; 0&#46;05 comparing with control group</span>&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">ALT&#44; AST&#44; TC&#44; and TG levels in serum and TC and TG levels in liver tissues&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "t0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Gene&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">mRNA level<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Protein level <a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HCBP6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Group 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;69 &#177; 0&#46;08 <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;274 &#177; 0&#46;034 <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Group 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;63 &#177; 0&#46;10 <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;217 &#177; 0&#46;033 <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;11 &#177; 0&#46;19&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;540 &#177; 0&#46;061&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">SREBP-lc&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">Group 1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">4&#46;08 &#177; 0&#46;79 <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t  " align="center" valign="\n
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          "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">HCBP6 and SREBP-1c expressions in hepatocytes of Group 1&#44; Group 2&#44; and control rats&#46;</p>"
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Article information

ISSN: 16652681
Original language: English

DOI:10.5604/01.3001.0011.7396

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	7	0	7
2024 October	12	2	14
2024 September	18	0	18
2024 August	18	4	22
2024 July	22	4	26
2024 June	13	4	17
2024 May	15	3	18
2024 April	20	4	24
2024 March	24	3	27
2024 February	31	8	39
2024 January	16	3	19
2023 December	11	5	16
2023 November	15	7	22
2023 October	13	10	23
2023 September	9	3	12
2023 August	16	2	18
2023 July	22	2	24
2023 June	28	3	31
2023 May	45	0	45
2023 April	52	3	55
2023 March	38	1	39
2023 February	18	2	20
2023 January	13	4	17
2022 December	33	7	40
2022 November	39	4	43
2022 October	26	13	39
2022 September	27	24	51
2022 August	56	10	66
2022 July	57	5	62
2022 June	19	10	29
2022 May	24	10	34
2022 April	19	9	28
2022 March	35	10	45
2022 February	45	6	51
2022 January	54	5	59
2021 December	38	11	49
2021 November	35	11	46
2021 October	34	9	43
2021 September	15	10	25
2021 August	11	9	20
2021 July	22	8	30
2021 June	21	10	31
2021 May	18	9	27
2021 April	53	4	57
2021 March	28	7	35
2021 February	18	7	25
2021 January	12	11	23
2020 December	14	5	19
2020 November	28	8	36
2020 October	12	2	14
2020 September	17	10	27
2020 August	26	6	32
2020 July	29	11	40
2020 June	36	2	38
2020 May	18	8	26
2020 April	13	2	15
2020 March	21	0	21
2020 February	14	5	19
2020 January	21	7	28
2019 December	24	6	30
2019 November	15	4	19
2019 October	14	1	15
2019 September	29	2	31
2019 August	9	3	12
2019 July	7	9	16
2019 June	15	2	17
2019 May	14	9	23

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