Chronic-binge ethanol feeding aggravates systemic dyslipidemia in Ldlr-/- mice, thereby accelerating hepatic fibrosis

作者：Constanze Hoebinger, Dragana Rajcic, Beatriz Silva, Tim Hendrikx · 发表于：Frontiers in Endocrinology · 年份：2023 · DOI：10.3389/fendo.2023.1148827 · 被引用次数：9 · 研究领域：Alcohol Consumption and Health Effects、Liver Disease Diagnosis and Treatment、Liver physiology and pathology

Objective Chronic ethanol consumption is known to cause alcohol-associated liver disease, which poses a global health concern as almost a quarter of heavy drinkers develop severe liver damage. Alcohol-induced liver disease ranges from a mild, reversible steatotic liver to alcoholic steatohepatitis and irreversible liver fibrosis and cirrhosis, ultimately requiring liver transplantation. While ethanol consumption is associated with dysregulated lipid metabolism and altered cholesterol homeostasis, the impact of dyslipidemia and pre-existing hypercholesterolemia on the development of alcohol-associated liver disease remains to be elucidated. Design To address the influence of systemic dyslipidemia on ethanol-induced liver disease, chronic-binge ethanol feeding was applied to female C57BL/6J (wild type) mice and mice deficient for the low-density lipoprotein receptor ( Ldlr -/- ), which display a human-like lipoprotein profile with elevated cholesterol and triglyceride levels in circulation. Respective control groups were pair-fed an isocaloric diet. Results Chronic-binge ethanol feeding did not alter systemic lipid levels in wild type mice. While increased systemic cholesterol levels in Ldlr -/- mice were not affected by ethanol feeding, chronic-binge ethanol diet aggravated elevated plasma triglyceride levels in Ldlr -/- mice. Despite higher circulatory triglyceride levels in Ldlr -/- mice, hepatic lipid levels and the development of hepatic steatosis were not different from w...