Nicotinamide Riboside Ameliorates Fructose-Induced Lipid Metabolism Disorders in Mice by Activating Browning of WAT, and May Be Also Related to the Regulation of Gut Microbiota

Objectives: This study aims to observe the preventive effect of nicotinamide riboside (NR) on fructose-induced lipid metabolism disorders and explore its mechanism. Methods: Male C57BL/6J mice were fed a 20% fructose solution and given 400 mg/kg NR daily by gavage for 10 weeks. Results: The results indicated that NR supplementation significantly reduced the body weight, liver weight, white adipose tissue (WAT) weight, serum, and hepatic lipid levels. NR upregulated the protein expression levels of sirtuin-1 (SIRT1), AMP-activated protein kinase (AMPK), PR domain containing 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor-gamma coactiva-tor-1-alpha (PGC-1 alpha), nuclear respiratory factor 1-encoding gene (NRF1), mitochondrial transcription factor A (TFAM), cluster of differentiation 137 (CD137), transmembrane protein 26 (TMEM26), and T-box 1 (TBX1). Moreover, NR enhanced the Actinobacteria and Enterorhabdus abundance. Spearman's correlation analysis revealed that significant correlations exist between Firmicutes, Bacteroidetes, and Erysipelotrichaceae with browning-related indicators. Conclusions: In conclusion, NR could alleviate lipid metabolic abnormalities induced by fructose through activating SIRT1/AMPK-mediated browning of WAT. The mechanism by which NR improves fructose-induced lipid metabolism disorders may also be associated with the modulation of intestinal flora.