P-2 DE NOVO LIPOGENESIS MARKERS ARE INVOLVED IN METABOLIC ASSOCIATED FATTY LIVER DISEASE PROGRESSION IN BTBR OB/OB MICE
Lucas Opazo-Rios1,2, Manuel Soto-Catalan1, Iolanda Lázaro3, Aleix Sala-Vila3, Cristian Pérez-Gallardo4, Fabian Segovia-Miranda4, Juan Antonio Moreno5, Jesús Egido1, Sebastián Mas-Fontao1
1 Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28040 Madrid, Spain
2 Facultad de Ciencias de la Salud, Universidad de Las Américas, 4301099, Concepción-Talcahuano, Chile
3 Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain
4 Department of Cell Biology, Faculty of Biological Sciences, Universidad de Concepción, Concepción, Chile
5 Department of Cell Biology, Physiology and Immunology, University of Cordoba; Maimonides Biomedical Research Institute of Cordoba (IMIBIC); UGC Nephrology, Hospital Universitario Reina Sofía, 14004 Cordoba, Spain
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MAFLD is a hepatic manifestation of metabolic syndrome and is usually associated with obesity and type 2 diabetes, excluding other causes not associated with positive energy balance. This study aimed to characterize the pathophysiological mechanism involved in MAFLD development in susceptible-strain Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob).</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Materials and Methods</span><p id="spara002" class="elsevierStyleSimplePara elsevierViewall">We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4-22 weeks. The lipid composition was assessed and lipid-related pathways were studied at transcriptional and protein levels.</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Results</span><p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Microvesicular steatosis was evident in BTBR ob/ob from week 6, progressing to macrovesicular in the following weeks. At the 12th week, inflammatory clusters, activation of STAT3 and Nrf2 signaling pathways, and hepatocellular ballooning. At 22 weeks, the histopathological features previously observed were maintained and no signs of fibrosis were detected. Liver gene-expression analysis demonstrated modifications in fatty acid transporters associated with uptake (Cd36, Cd204, Fatp4)/efflux (Abca1, Abcg1), <span class="elsevierStyleItalic">de novo</span> fatty acid synthesis enzymes (ACC, FASN, SCD-1) and transcription factors related to lipogenic pathways (Pparα/γ, Srebp-1, Chrebp-1). Additionally, the lipidomic analysis showed profiles associated with de novo lipogenesis (DNL), showing a significant increase in palmitic acid (C16:0), palmitoleic acid (C16:1n7) and oleic acid (C18:1n9).</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Conclusions</span><p id="spara004" class="elsevierStyleSimplePara elsevierViewall">BTBR ob/ob mice develop MAFLD profiles that resemble pathological features observed in humans, with overactivation of inflammatory response, oxidative stress and DNL signaling pathways. Therefore, BTBR ob/ob mouse is an excellent model for the study of the steatosis to steatohepatitis transition.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0001" "titulo" => "Introduction and Objectives" ] 1 => array:2 [ "identificador" => "abss0002" "titulo" => "Materials and Methods" ] 2 => array:2 [ "identificador" => "abss0003" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abss0004" "titulo" => "Conclusions" ] ] ] ] "multimedia" => array:1 [ 0 => array:6 [ "identificador" => "fig0001" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1093 "Ancho" => 1667 "Tamanyo" => 230500 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Unlabelled imag" "rol" => "short" ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/00000028000000S1/v2_202308150516/S1665268123000108/v2_202308150516/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/16652681/00000028000000S1/v2_202308150516/S1665268123000108/v2_202308150516/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268123000108?idApp=UINPBA00004N" ]
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