Overexpression of NRK1 ameliorates diet- and age-induced hepatic steatosis and insulin resistance

• DOI: 10.1016/j.bbrc.2018.04.107
• Publication Date: 2018-04-30T09:30:22Z
• Authors: Rui Fan; Jing Cui; Feng Ren; Qingzhi Wang; Yanmei Huang; Bin Zhao; Lai Wei; Xinlai Qian; Xiwen Xiong
• Keywords: Male; Niacinamide; 0301 basic medicine; Aging; Pyridinium Compounds; Diet, High-Fat; Lipid Metabolism; NAD; 3. Good health; Fatty Liver; Mice, Inbred C57BL; Mice; Phosphotransferases (Alcohol Group Acceptor); 03 medical and health sciences; HEK293 Cells; Liver; NIH 3T3 Cells; Animals; Humans; Insulin Resistance; Triglycerides

NAD+ is a co-enzyme in redox reactions and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Dietary supplementation of NAD+ precursors nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR) protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we sought to identify the roles of nicotinamide riboside kinase 1 (NRK1) plays in regulating hepatic NAD+ biosynthesis and lipid metabolism. Using adenovirus mediated gene transduction to overexpress or knockdown NRK1 in mouse liver, we have demonstrated that NRK1 is critical for maintaining hepatic NAD+ levels and triglyceride content. We have further shown that the hepatic expression of Nmrk1 mRNA is significantly decreased either in mice treated with high-fat diet or in aged mice. However, adenoviral delivery of NRK1 in these diet- and age-induced mice elevates hepatic NAD+ levels, reduces hepatic steatosis, and improves glucose tolerance and insulin sensitivity. Our results provide important insights in targeting NRK1 for treating hepatic steatosis.