학술논문

Leptin Regulates Hypercholesterolemia in Alcoholic Liver Disease
Document Type
Academic Journal
Source
Indian Journal of Clinical Biochemistry. May 24, 2022, Vol. 30 Issue S1, pS28, 1 p.
Subject
Protein binding
Leptin
Hypercholesterolemia
Cholesterol
Monounsaturated fatty acids
Liver cirrhosis
Language
English
ISSN
0970-1915
Abstract
O05 V. Balasubramaniyan1,2 and N. Nalini2 (1) Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry-605006, India. (2) Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram-608002, [...]
Alcohol induced fatty liver disease is the most common and earliest response to the progression of fibrosis, cirrhosis and/or hepatocellular carcinoma. The mechanism by which ethanol causes fatty liver disease is complex and not fully understood, however, enhanced hepatic lipogenesis has been proposed as an important biochemical mechanism. We have previously noted that the potential preventive effect of leptin on alcohol elicited toxicity in in vitro. The purpose of this study was to evaluate the effect of leptin on ethanol induced elevated hepatic cholesterol synthesis and fatty acid composition in mice. CD-1 mice (n = 15/group) were studied for 45 days. Four groups were studied. 1) control, 2) leptin + control (230 [micro]g/kg intraperitoneal every alternate day from day 15), 3) alcohol (6.32 g/kg daily by gastric lavage, for 45 days) and 4) alcohol + leptin (as prior dosing). Compared to control, ethanol supplementation significantly (p < 0.05) increased % of palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1) and docosapentaenoic acid (22:5) levels, whereas palmitoleic acid (16:1) and arachidonic acid (20:4) concentrations were decreased significantly (p < 0.05). Leptin treatment to ethanol fed mice significantly corrects the above indices. Furthermore, leptin administration significantly down regulates ethanol induced plasma total and ester cholesterol and hepatic HMG CoA reductase, cholesterol ester synthase and sterol regulatory element binding protein 2 protein expression. The activities of hepatic lipoprotein lipase, plasma lecithin cholesterol acyl transferase and hepatic cholesterol ester hydrolase were significantly (p < 0.05) lowered following ethanol supplementation compared to control mice. These features were significantly (p < 0.05) increased by addition of leptin. Liver histology showed that mice given ethanol had macro and micro vesicular steatosis. However, ethanol + leptin treated liver showed sinusoidal dilatation and no fatty change. Conclusion: Thus, administration of exogenous leptin to alcohol fed mice significantly decreased hepatic cholesterol accumulation and also regulates fatty acid composition; warranting population based further mechanistic studies.