The protective effect of nicotinamide riboside against age-induced hepatic disease in mice

Background & Aims. Aging is one of the key triggers of non-alcoholic fatty liver disease (NAFLD). Yet, the pathomechanism of the age-associated NAFLD is not fully understood. Nicotinamide adenine dinucleotide (NAD), an ubiquitous coenzyme, has beneficial effects on aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of age-induced NAFLD. Methods. NR supplied food (2.5g/kg food) was applied to aged mice for three months. Changes of body weight, food intake, hepar weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammation infiltrated. Results. NR significantly reduced fat pat mass, lipid content and AST in aged mice, but didn't modify in terms of body weight, food intake, hepar weight and ALT in aged mice. Given normal chow, aged mice displayed decline of NAD concentration. In aged mice model, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis (Masson's trichrome staining and TGF-β staining) were observed in liver. In addition, Kupffer cells accumulated and pro-inflammatory cytokines expression were more aggravated in hepatic tissues. Whereas, NR administration completely corrected these NAFLD phenotypes and inflammation infiltrated in liver. Conclusion. NR has benefits on age-associated lipid accumulation and hepatic steatosis, and the oral uptake of NR may be a promising strategy to prevent the progression of NAFLD.