Key Findings
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide that is characterized by hepatocyte triacylglycerol accumulation (steatosis), which can progress to nonalcoholic steatohepatitis (NASH) or cirrhosis. N-3 polyunsaturated fatty acids (PUFAs) might be beneficial in the treatment of NAFLD. This study assessed the potential role of flaxseed oil on symptoms of NAFLD. The study determined the effects of dietary supplementation of flaxseed oil on NAFLD induced by western-type high-fat and high-cholesterol diet (WTD) in apolipoprotein-E knockout (apoE-KO) mice and investigate the underlying molecular mechanisms. Flaxseed oil improved NAFLD induced by WTD via restoring impaired lipid metabolism, attenuating oxidative stress, and inhibiting inflammation. The flaxseed oil intervention decreased mRNA and protein expressions of SREBP-1c and ACC in liver. These results indicate that flaxseed oil supplementation may inhibit the SREBP-1c pathway to downregulate ACC expression, which in turn reduces TG synthesis. The authors suggested that improvement effects of flaxseed oil on lipid profiles and NAFLD may be linked to the regulation of SREBP-1c and PPARα. In the present study, ROS production and the lipid peroxidation indicator MDA were increased in both serum and liver tissue in WDT-fed mice, whereas the levels of GSH and SOD, two potent antioxidants, were decreased in both serum and liver tissue. However, a pronounced reduction of ROS along with lower concentration of MDA and higher levels of GSH and SOD were observed in FO-fed animals than in mice on WTD. These results suggested that the potential effect of flaxseed oil in preventing oxidative stress could be due to the ability to reduce free radical production or through increased free radical scavenging activity. Antioxidant potential of flaxseed oil may represent another mechanism for alleviating and improving NAFLD. The present study demonstrated that chronic WTD intake induced NAFLD. Dietary flaxseed oil compensated for WTD-induced lipid metabolism disorder, depressed hepatic oxidative stress, and inflammation, which contribute to the amelioration of NAFLD progress. The results suggest that flaxseed oil may be a potential dietary therapeutic tool against NAFLD.
ABSTRACT
The prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased globally during recent decades. Intake of n-3 polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α-linolenic acid (ALA, C18:3n-3), a plant-derived n-3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein-E knockout (apoE-KO) mice were given a normal chow diet, a western-type high-fat and high-cholesterol diet (WTD), or a WTD diet containing 10% flaxseed oil (WTD + FO) for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD-induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP-1c, ACC), triacylglycerol catabolism (PPARα, CPT1A, and ACOX1), inflammation (NF-κB, IL-6, TNF-α, and MCP-1), and oxidative stress (ROS, MDA, GSH, and SOD).
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