Sleeve gastrectomy ameliorated high-fat diet (HFD)-induced non-alcoholic fatty liver disease and upregulated the nicotinamide adenine dinucleotide +/ Sirtuin-1 pathway in mice |
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Authors: | Rong Hua Guan-Zhen Wang Qi-Wei Shen Ye-Ping Yang Meng Wang Meng Wu Yi-Kai Shao Min He Yi Zang Qi-Yuan Yao Zhao-Yun Zhang |
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Institution: | 1. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China;2. National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Shanghai, 201203, China;3. Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, 200040, China;4. Department of Endocrinology, The Second Affiliated Hospital, Soochow University, Suzhou, 215004, China |
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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.MethodsC57BL/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.ResultsSG 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.ConclusionSG significantly alleviated NAFLD in HFD-induced obese mice with increasing the hepatic NAD + levels and upregulating the NRK1/NAD+/SIRT1 pathway. |
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Keywords: | NAD+ NAFLD NRK1 SIRT1 Sleeve gastrectomy |
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