fk-866 and Non-alcoholic-Fatty-Liver-Disease

Nonalcoholic fatty liver disease is one of the most common liver diseases in the world and is a typical hepatic manifestation of metabolic syndrome which is characterized with lipid accumulation in liver. Nicotinamide phosphoribosyltransferase (NAMPT) has been recently identified as an enzyme involved in nicotinamide adenine dinucleotide (NAD. Hepatic steatosis model was induced by high fat diet (HFD) in C57BL/6 mice in vivo. HepG2 and Hep1-6 hepatocytes were transfected with NAMPT vector plasmid or treated with NAMPT inhibitor FK866 and then incubated with oleic acid. Lipids accumulation was examined by HE staining or oil red staining. Quantitative RT-PCR and Western blot were used to measure expressions of the genes involved in lipogenic synthesis.. FK866 significantly promoted liver steatosis in the mice fed with HFD and hepatic lipid accumulation in vitro, accompanied by the increases of the expressions of lipogenic genes such as sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN). Nicotinamide mononucleotide (NMN) and NAD. Our results demonstrated that inhibition of NAMPT aggravated the HFD- or oleic acid-induced hepatic steatosis through suppressing Sirt1-mediated signaling pathway. On the one hand, the inhibition of NAMPT reduced the production of NAD

Topics: Acrylamides; AMP-Activated Protein Kinases; Animals; Carbazoles; Cell Line; Cytokines; Diet, High-Fat; Enzyme Inhibitors; Gene Expression Regulation; Hep G2 Cells; Hepatocytes; Humans; Liver; Male; Mice; Mice, Inbred C57BL; NAD; Nicotinamide Mononucleotide; Nicotinamide Phosphoribosyltransferase; Non-alcoholic Fatty Liver Disease; Oleic Acid; Piperidines; Resveratrol; Signal Transduction; Sirtuin 1; Sterol Regulatory Element Binding Protein 1; Stilbenes