Journal Article

The Ameliorating Effects of n-3 Polyunsaturated Fatty Acids on Liver Steatosis Induced by a High-Fat Methionine Choline-Deficient Diet in Mice

Stránská, Milena, Stříteský, Jan, Šmíd, Václav, Vítek, Libor, Rubert, Josep, Stehnová, Kamila, Dvořák, Karel, Hajšlová, Jana, Brůha, Radan, Staňková, Barbora, Strnad, Hynek

2023

Overview

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism. On the contrary, a diet enriched with n-3 polyunsaturated fatty acids (n-3-PUFAs) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either a high-fat methionine choline-deficient diet (MCD) or standard chow with or without n-3-PUFAs. Liver histology, serum biochemistry, detailed plasma and liver lipidomic analyses, and genome-wide transcriptome analysis were performed. Mice fed an MCD developed histopathological changes characteristic of NAFLD, and these changes were ameliorated with n-3-PUFAs. Simultaneously, n-3-PUFAs decreased serum triacylglycerol and cholesterol concentrations as well as ALT and AST activities. N-3-PUFAs decreased serum concentrations of saturated and monounsaturated free fatty acids (FAs), while increasing serum concentrations of long-chain PUFAs. Furthermore, in the liver, the MCD significantly increased the hepatic triacylglycerol content, while the administration of n-3-PUFAs eliminated this effect. Administration of n-3-PUFAs led to significant beneficial differences in gene expression within biosynthetic pathways of cholesterol, FAs, and pro-inflammatory cytokines (IL-1 and TNF-α). To conclude, n-3-PUFA supplementation appears to represent a promising nutraceutical approach for the restoration of abnormalities in liver lipid metabolism and the prevention and treatment of NAFLD.

• Publisher: MDPI AG
• Subject: Animals / Apoptosis / Carbon / Cholesterol - metabolism / Choline - metabolism / Diet / Diet, High-Fat - adverse effects / Fatty acids / Fatty Acids, Nonesterified - metabolism / Fatty Acids, Omega-3 - metabolism / Fatty Acids, Omega-3 - pharmacology / Fatty Acids, Omega-3 - therapeutic use / Fatty Acids, Unsaturated - metabolism / Fatty liver / Lipids / Liver - metabolism / Liver diseases / Metabolism / Methionine - metabolism / Mice / Mice, Inbred C57BL / Non-alcoholic Fatty Liver Disease - etiology / Non-alcoholic Fatty Liver Disease - genetics / Oxidative stress / Polyunsaturated fatty acids / Racemethionine - metabolism / Racemethionine - pharmacology / Triglycerides - metabolism