Tetrahydrocurcumin protects against nonalcoholic fatty liver disease by improving lipid metabolism and redox homeostasis.

[Display omitted] • Tetrahydrocurcumin (THC) improves glucose and lipid metabolism disorders in nonalcoholic fatty liver disease (NAFLD) in mice. • THC regulates the expression of oxidoreductase genes and lipid-metabolizing enzyme genes in the liver of NAFLD mice. • THC increases the antioxidant capacity and inhibits lipid deposition in HepG2 cells by activating the NRF2 signaling pathway. Nonalcoholic fatty liver disease (NAFLD) is the most common liver metabolic disease in the world. In this study we investigated the effect of tetrahydrocurcumin (THC), a potent antioxidant, on NAFLD. We found that THC significantly reduced the body weight, serum and liver lipids, serum malondialdehyde (MDA) and fasting blood glucose (FBG) of male NAFLD mice induced by feeding a high-fat diet (HFD) for 8 weeks. A RNA-seq analysis revealed that THC also affected the expression of many genes involved in lipid metabolism in the liver of NAFLD mice, including increasing the mRNA expression of CYP51 and FOXQ1. Moreover, THC significantly reduced sodium oleate-induced lipid accumulation, activated the NRF2 pathway, and up-regulated the mRNA expression of FGF21 in HepG2 cells. Overall, our study showed that THC can improve the antioxidant capacity of liver, which suggests that dietary THC may be used to treat NAFLD. [ABSTRACT FROM AUTHOR]