Sleeve Gastrectomy Ameliorated High-Fat Diet (Hfd)-Induced Non-Alcoholic Fatty Liver Disease And Upregulated The Nicotinamide Adenine Dinucleotide +/Sirtuin-1 Pathway In Mice

Background: /Objective: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and effective treatments are lacking. Bariatric surgery, including sleeve gastrectomy (SG), is a potential therapeutic strategy for NAFLD, but the molecular mechanisms underlying its effects are not fully understood. In this study, the effects of SG and the underlying mechanisms were evaluated in a mouse model of high-fat diet (HFD)-induced NAFLD.Methods: C57BL/6 mice were randomly divided into three groups: normal diet with sham operation (NC Sham group), HFD with sham operation (HFD-Sham group), and HFD with sleeve gastrectomy (HFD-SG group). Glucose metabolism and fat accumulation in the body and liver were analyzed before and after SG. Lipid metabolism and inflammation in the liver were evaluated. Nicotinamide adenine dinucleotide (NAD+) levels as well as nicotinamide riboside kinase (NRK1) and Sirtuin-1 (SIRT1) expression levels were evaluated.Results: SG attenuated the HFD-induced increases in glucose and insulin levels, fat accumulation, and lipid droplet accumulation. Fatty acid biosynthesis, the expression of the metabolism-related genes ACC1, FASN, SCD1, and DGAT1, and the levels of inflammatory factors were higher in HFD mice than in NC mice and decreased after SG. NAD + concentrations were 54.9 +/- 13.4 mmol/mg in NC-Sham mice, 37.6 +/- 8.1 mmol/mg in HFD-Sham mice, and 79.9 +/- 13.0 mmol/mg in HFD-SG mice (p < 0.05). NRK1 and SIRT1 expression increased dramatically after SG at both the RNA and protein levels.Conclusion: SG significantly alleviated NAFLD in HFD-induced obese mice with increasing the hepatic NAD + levels and upregulating the NRK1/NAD+/SIRT1 pathway. (C) 2020 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V.