Grape Extract Activates Brown Adipose Tissue Through Pathway Involving the Regulation of Gut Microbiota and Bile Acid

Abstract

Scope: Although the physiological function of grape extract (GE) has long been recognized, the precise mechanism remains obscure. This study is designed to investigate the effects of GE on metabolism and the association between GE activation of brown adipose tissue (BAT) and the restoration of gut microbiota (GM).

Methods and results: Diet-induced obese mice are used to investigate the function of GE. GE administration increases energy metabolism and prevents obesity. Also, GE restores the dysbiosis of GM by augmenting the observed species, enhancing the Firmicutes-to-Bacteroidetes ratio and increasing the abundance of the Bifidobacteria, Akkermansia, and Clostridia genera. This restoration of GM alters the bile acid (BA) pool in the serum. The abundance of Akkermansia, Clostridium, and Bifidobacterium is negatively correlated with the concentrations of TαMCA, TβMCA, and TCA but is positively correlated with DCA. The changes in BA promoted TGR5 in BAT, which contributed to thermogenesis. The metabolites of GE in blood do not stimulate TGR5 in vitro.

Conclusion: GE stimulates the thermogenesis of BAT through a pathway involving the regulation of GM and BA in diet-induced obese mice. This study reveals the mechanism by which dietary polyphenols promote thermogenesis by regulating BA, which is altered by GM.

Keywords: TGR5; bile acid; brown adipose tissue; grape extract; gut microbiota.