Poster Topical Area: Biomarkers
Poster Board Number: 144
Objectives: Hepatic steatosis is the initial stage of Non-alcoholic fatty liver disease (NAFLD), which promotes insulin resistance and type 2 diabetes. Docosahexaenoic acid (DHA; C22; Ω-3) shows beneficial effects on NAFLD. The protein deacetylase Sirtuin1 (SIRT1) increases energy metabolism and decreases lipogenesis. Here, we investigated whether DHA plays a role in protecting against hepatic steatosis via SIRT1 activation.
Methods: Both in vivo and in vitro hepatic steatosis models were used: diet-induced obesity (DIO) model (middle-aged male C57BL/6 mice fed a high-fat diet (HFD)) and palmitic acid (PA)-induced lipid accumulation cell model (HepG2 cells). Livers and cells were harvested for histological, gene and protein expression analysis. The effects of DHA on lipogenesis, fatty acid (FA) oxidation and inflammation in liver cells were studied. The role of SIRT1 on these effects was also studied through gene knockdown or inhibitor sirtinol.
Results: In DIO mice, treatment with DHA for 8 weeks (twice a week administrated by gavage) inhibited the lipid accumulation, increased 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 attenuated by lentivirus-mediated SIRT1 knockdown, accompanied with increased expression of markers of lipogenesis, inflammation and reduced fatty acid oxidation. In HepG2 cells, DHA prevented PA-induced lipid droplets accumulation, 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.
Conclusions: DHA ameliorates hepatic steatosis and reduced inflammation of liver in obese middle-aged mice by mechanisms involving SIRT1 activation. The results of this study will increase the understanding of mechanisms of DHA in regulating hepatic steatosis and provide new nutritional strategies.
Xi’an Jiaotong University Health Science Center
Xi'an, Shaanxi, China (People's Republic)