Methyl-group donor supplementation beneficial effects on metabolic, histological, and inflammatory parameters in a murine model of alcoholic steatohepatitis

Introduction and Objectives

Chronic alcohol consumption is the main cause of alcohol-related liver disease (ARLD) ranging a spectrum characterized by inflammation and progressive fibrosis. Currently, abstinence is the main treatment for ARLD; for this reason, it becomes indispensable to evaluate therapeutic alternatives as methyl group donors which have the potential to influence the development and progression of the disease. To evaluate the effect of chronic alcohol consumption coupled with methyl-group donor supplementation on metabolic and histologic features and gene expression of proinflammatory cytokines in a murine model of ARLD.

Materials and Patients

: 24 male C57BLC/6J mice divided into groups with conventional diet (ND n=8); alcohol-induced liver-injury induced with ad libitum consumption of a 20% ethanol-aqueous drink and a 45%-fat diet (OH n=8) for 18 weeks; or latter diet for 10 weeks, plus 8 weeks of this diet and methyl group (OH +METMIX n=8). This protocol is in the process of being approved by the CUCS Ethics, Research and Biosafety Committees.

Results

Serum biochemical studies and histological analysis performed in the methyl-donor supplemented group (OH+ METMIX) -zinc sulfate, methionine, vitamin B12, folic acid, betaine and choline- showed a significant decrease in body weight, epididymal and visceral fat (p<0.05), and serum levels of cholesterol, HDL and LDL. Whilst, serum levels of AST, ALT, TG and VLDL, as well as IL-6 and TNF-α mRNA from hepatic tissue, and the hormones insulin, leptin, glucagon, and resistance, demonstrated a tendency to decrease their concentrations compared to the OH group.

Conclusions

Treatment with methyl-group donors improves body weight, body composition, cholesterol, LDL and HDL concentrations, exerting beneficial and protective effects even when consuming an ethanol-aqueous drink.

Ethical statement

The protocol was registered and approved by the Ethics Committee.

Declaration of interests

None

Funding

This study was supported by the “Programa de Fortalecimiento de la Investigación y el Posgrado 2022” of the “Universidad de Guadalajara”.