Bavachin ameliorates HFD-induced obesity through enhancing gut microbiota-regulated adipose thermogenesis

Promising approaches to combat obesity through dissipating energy are offered via activating thermogenic programs in brown adipose tissue (BAT). Bavachin (Bav) is a naturally occurring flavonoid isolated from the seeds and fruits of Psoralea corylifolia L., a functional food and also a traditional herbal medicine, which may ameliorate obesity. Here, the effects of Bav on the activation of BAT were investigated in high-fat-diet (HFD)-fed mice. Here, our results showed that Bav for 12 weeks significantly inhibited body weight gain, alleviated blood glucose/lipid levels, and reduced lipid accumulation in BAT. Importantly, Bav upregulated the expression of uncoupling protein 1 (UCP1) and other thermogenic factors in BAT and inguinal white adipose tissue (iWAT). Further microbiota analysis revealed that Bav restored HFD-evoked microbial dysbiosis and Spearman correlation showed specific bacterial communities such as Bacteroidetes, Firmicutes, Lactobacillus, unitified_Clostridia, Romboutsia, and Ligilactobacillus strongly associated with obesity-related traits and brown markers. Importantly, Bav markedly increased the fetal concentration of short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, enhanced SCFAs-producing enzymes (acetate kinase (Ack), methylmalonyl-CoA decarboxylase (Mcd) and butyryl-CoA (But), and upregulated the free fatty acid receptor 2 (GRP43) in colon, iWAT, and BAT. Collectively, our findings revealed that Bav alleviated obesity via activations of BAT and WAT browning, which may be associated with gut microflora-regulated SCFAs production.