Inhibition of ceramide de novo synthesis reduces liver lipid accumulation in rats with nonalcoholic fatty liver disease.

Abstract

BACKGROUND & AIMS:

Nonalcoholic fatty liver disease (NAFLD) is an insulin resistance-related hepatic disorder which can transform to cirrhosis. Insulin resistance deregulates hepatic lipid metabolism, leading to accumulation of cytotoxic lipids including ceramide and diacylglycerols. Myriocin, obtained from fungi traditionally used in Chinese medicine in an effort to attain eternal youth, is a potent pharmacological inhibitor of ceramide de novo synthesis. We examined whether inhibition of ceramide de novo synthesis with myriocin ameliorate hepatic lipid accumulation and reverse NAFLD.

METHODS:

The experiment was carried out on male Wistar rats. The animals were divided into four groups: (i) control group, fed standard rodent diet, (ii) group, fed standard diet also treated with myriocin for 7 days, (iii) group, fed high-fat diet for 5 weeks, (iv) group, fed high-fat diet and treated with myriocin. In liver samples sphingolipids: ceramide, sphingosine and sphingosine-1-phosphatate and neutral lipids, such as diacylglycerols and triacylglycerols were measured. In peripheral blood samples, glucose and insulin levels and aminotransferases activities were measured.

RESULTS:

High-fat diet feeding caused NAFLD, confirmed by histological assessment, with increased hepatic lipids accumulation and whole-body insulin resistance. After treating with inhibitor of ceramide de novo synthesis, decrease in hepatic ceramide and other toxic lipids were noticed. Moreover, histological analysis of liver samples revealed that inhibition of ceramide de novo synthesis reduced hepatic steatosis.

CONCLUSIONS:

Inhibition of ceramide de novo synthesis reduced hepatic lipid accumulation in rats with NAFLD, this led to amelioration of hepatic steatosis.

• Authors: Krzysztof Kurek, Dominika M Piotrowska, Patrycja Wiesiołek-Kurek, Bartłomiej Łukaszuk, Adrian Chabowski, Jan Górski, Małgorzata Zendzian-Piotrowska
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 34 Issue 7 Pg. 1074-83 (Aug 2014) ISSN: 1478-3231 [Electronic] United States
• PMID: 24106929 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Blood Glucose
• Ceramides
• Fatty Acids, Monounsaturated
• Insulin
• Transaminases
• thermozymocidin

Topics

• Analysis of Variance
• Animals
• Biosynthetic Pathways (drug effects)
• Blood Glucose (metabolism)
• Ceramides (biosynthesis)
• Chromatography, High Pressure Liquid
• Fatty Acids, Monounsaturated (pharmacology, therapeutic use)
• Insulin (blood)
• Lipid Metabolism (drug effects)
• Liver (drug effects)
• Male
• Non-alcoholic Fatty Liver Disease (drug therapy)
• Rats
• Rats, Wistar
• Scintillation Counting
• Transaminases (blood)