Tectorigenin ameliorated high-fat diet-induced nonalcoholic fatty liver disease through anti-inflammation and modulating gut microbiota in mice

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a complex pathogenesis of liver disease combined with liver inflammation and gut microbiota dysbiosis. Tectorigenin (Tg) is derived from many plants with excellent anti-inflammation activity. However, the beneficial effect of Tg on NAFLD associated with gut microbiota remained unclear. This study aimed to investigate the underlying beneficial effect of Tg on NAFLD in high-fat diet (HFD)-fed mice. Results showed that Tg alleviated lipid profiles and liver steatosis, and reduced serum lipopolysaccharide (LPS) and total bile acid (TBA) levels. Besides, RT-qPCR and Western blot suggested that Tg alleviated hepatic lipid accumulation through inhibiting the lipogenesis and promoting the lipolysis, prevented gut-derived LPS-induced liver inflammatory via restoring intestinal barrier and restraining pro-inflammatory cytokines release, meanwhile, promoted the BA circulation via activating BA receptor and promoting BA synthesis. Moreover, Tg reverted the HFD-induced gut microbial dysbiosis by promoting the growth of beneficial Akkermansia, and inhibiting the proportions of harmful microbes, including Blautia, Lachnoclostridium, Lachnospiraceae_UCG-006, Roseburia, Romboutsia and Faecalibaculum, which were highly correlated with NAFLD-related parameters in serum and liver. Thus, Tg could attenuate NAFLD through mediating the liver-gut axis, and it could be used as a dietary supplement for NAFLD treatment via its anti-inflammatory and prebiotic effects.