Bacteroides spp. promotes branched-chain amino acid catabolism in brown fat and inhibits obesity

The gut microbiome has emerged as a key regulator of obesity; however, its role in brown adipose tissue (BAT) metabolism and association with obesity remain to be elucidated. We found that the levels of circulating branched-chain amino acids (BCAA) and their cognate alpha-ketoacids (BCKA) were significantly correlated with the body weight in humans and mice and that BCAA catabolic defects in BAT were associated with obesity in diet-induced obesity (DIO) mice. Pharmacological systemic enhancement of BCAA catabolic activity reduced plasma BCAA and BCKA levels and protected against obesity; these effects were reduced in BATectomized mice. DIO mice gavaged with Bacteroides dorei and Bacteroides vulgatus exhibited improved BAT BCAA catabolism and attenuated body weight gain, which were not observed in BATectomized DIO mice. Our data have highlighted a possible link between the gut microbiota and BAT BCAA catabolism and suggest that Bacteroides probiotics could be used for treating obesity.

Automated summary

The gut microbiome plays a key role in regulating obesity, with BCAA metabolism in brown adipose tissue (BAT) being a potential target for addressing obesity. Modulating BCAA catabolism in BAT through pharmacological interventions and gut microbiota manipulation could offer therapeutic strategies against obesity.