Garcinol Reduces Obesity in High‐Fat‐Diet‐Fed Mice by Modulating Gut Microbiota Composition

SCOPE: Obesity has become a major health problem worldwide and is associated with low-grade chronic inflammation and intestinal dysbiosis. This study is conducted to investigate the chemopreventive effects of garcinol, a polyisoprenylated benzophenone derivative isolated from the fruit rind of Garcinia indica. How garcinol protects against obesity in high-fat diet (HFD)-induced mice is delineated and whether its anti-obesity effects are related to gut microbiota has been determined. METHODS AND RESULTS: The results show that garcinol reduces HFD-fed mice body weight gain and relative visceral adipose tissue fat weight in a dose-dependent manner. Furthermore, garcinol markedly reduces the plasma levels of glutamate pyruvate transaminase, total cholesterol, and triacylglycerol. The 16S rRNA gene sequence data indicate that garcinol not only reverses HFD-induced gut dysbiosis-as indicated by the decreased Firmicutes-to-Bacteroidetes ratios-but also controls inflammation by increasing the intestinal commensal bacteria, Akkermansia. In addition, the AMP-activated protein kinase α signaling pathway involved in adipocyte adipogenesis is also affected by garcinol. CONCLUSION: Taken together, these results demonstrate for the first time that garcinol can prevent HFD-induced obesity and may be used as a novel gut microbiota modulator to prevent HFD-induced gut dysbiosis and obesity-related metabolic disorders.