Sleeve gastrectomy ameliorated high-fat diet (HFD)-induced non-alcoholic fatty liver disease and upregulated the nicotinamide adenine dinucleotide +/ Sirtuin-1 pathway in mice

Asian J Surg. 2021 Jan;44(1):213-220. doi: 10.1016/j.asjsur.2020.05.030. Epub 2020 Jul 22.

Abstract

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 μmol/mg in NC-Sham mice, 37.6 ± 8.1 μmol/mg in HFD-Sham mice, and 79.9 ± 13.0 μmol/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.

Keywords: NAD+; NAFLD; NRK1; SIRT1; Sleeve gastrectomy.

MeSH terms

  • Animals
  • Bariatric Surgery / methods*
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Gastrectomy / methods*
  • Gene Expression / genetics*
  • Male
  • Mice, Inbred C57BL
  • NAD / metabolism*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / surgery*
  • Signal Transduction / genetics*
  • Sirtuin 1 / metabolism*
  • Up-Regulation / genetics*

Substances

  • NAD
  • Sirt1 protein, mouse
  • Sirtuin 1