<p>DHA Protects Against Hepatic Steatosis by Activating Sirt1 in a High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model</p>

Abstract

Docosahexaenoic acid (DHA; C22; n-3) shows beneficial effects on Non-alcoholic fatty liver disease (NAFLD). Deacetylase Sirtuin1 (Sirt1) was reported to increase energy metabolism and decrease lipogenesis. Here, we investigated whether DHA plays a role in protecting against hepatic steatosis via Sirt1. Main Methods: Both in vivo and in vitro hepatic steatosis models were used: diet-induced obesity (DIO) model (middle-aged C57BL/6 mice fed a high-fat diet (HFD)) and palmitic acid (PA)-induced lipid accumulation cell model (HepG2 cells). Key Findings: In DIO mice, treatment with DHA (gavage supplementation) for 8 weeks not only inhibited the lipid accumulation, but also increased fatty acids (FA) oxidation and induced triglyceride export in liver. These changes were accompanied by attenuation of inflammation. Moreover, DHA reversed the HFD-induced reduction of Sirt1 in liver. Interestingly, the beneficial effects of DHA were reversed by lentivirus-mediated Sirt1 knockdown, accompanied with increased expression of markers of lipogenesis, inflammation and reduced FA oxidation. In HepG2 cells, DHA prevented the accumulation of PA-induced lipid droplets, the decrease of FA oxidation and the reduction of Sirt1 level. Inhibition of Sirt1 by sirtinol partially reversed the beneficial effects of DHA on PA-treated cells. Significance: DHA alleviated hepatic steatosis and reduced inflammation of liver in obese middle-aged mice by mechanisms involving Sirt1 activation.

Maternal exercise conveys protection against NAFLD in the offspring via hepatic metabolic programming

“…Apart from the aforementioned mechanisms enhanced activation of mitochondrial biogenesis has been also discussed to be associated with prevention of NAFLD 41 . Recent studies demonstrated that hepatic PGC1α-overexpression, which was also found in our INT-offspring at P21, results in increased hepatic fatty acid oxidation and reduced triacylglycerol accumulation and presumably protects against the development of hepatic steatosis 12 , 42 – 44 . Even though Tfam mRNA-expression did not differ between CO- and INT-offspring at P21, the observed Pgc1α upregulation, the activation of KEGG—pathway “oxidative phosphorylation” and the fact that Pgc1α methylation due to exercise were also observed in other organs prompted us to perform methylation analysis of the Pgc1α promoter region at P21.…”

Maternal DHA Supplementation during Pregnancy and Lactation in the Rat Protects the Offspring against High-Calorie Diet-Induced Hepatic Steatosis

“…It has been shown that DHA supplementation in parallel with high-calorie feeding protects against the development of obesity-associated liver steatosis [ 34 , 35 ]. Therefore, in order to further investigate the beneficial effects of maternal DHA supplementation, we assessed the accumulation of triglycerides and cholesterol in liver samples from our four experimental groups.…”

Effects of Lactobacillus fermentum CQPC04 on Lipid Reduction in C57BL/6J Mice

“…A high-energy diet will not only cause a large amount of fat accumulation, resulting in an imbalance in lipid metabolism, but it will also affect the body's redox balance (Luo et al, 2020). A high-energy diet induces hyperglycemia through lipid metabolism and sugar metabolism and, subsequently, releases a large amount of free radicals, triggering oxidative stress (Park et al, 2020).…”