Jiangtang Tiaozhi Formula alleviates obesity by enhancing adipose thermogenesis via TGR5-mediated gut-liver-adipose axis.

BACKGROUND

Development of safe and effective anti-obesity drugs has emerged as an urgently needed issue. Jiangtang Tiaozhi Formula (JTTZF), a traditional Chinese medicine formulation, has demonstrated potential antidiabetic and hypolipidemic properties. However, the anti-obesity efficacy of JTTZF and its mechanisms remain insufficiently understood.

METHODS

We assessed the pharmacodynamic effects of JTTZF in diet-induced obese (DIO) mice, as well as in HepG2 cells and adipocytes, focusing on body weight and glucose/lipid metabolism in vivo and in vitro, respectively. 16S rDNA sequencing profiling and fecal microbiota transplantation (FMT) were applied to validate the contribution of gut microbiota in anti-obesogenic effects of JTTZF. Untargeted fecal metabolomics was utilized to explore the potential metabolic pathways mediating gut-liver-adipose axis leading to anti-obesity effect of JTTZF via thermogenesis, which were subsequently confirmed by qPCR detection.

RESULTS

JTTZF exhibited a significant effect of anti-obesity and metabolic benefit, including inhibiting weight gain and adiposity, reducing blood glycolipid, ameliorating glucose intolerance and insulin resistance, together with protecting against hepatic steatosis, compared with orlistat. Mechanistically, JTTZF boosted white fat browning and brown fat thermogenesis. More importantly, JTTZF remodeled gut microbiota by enhancing the colonization of beneficial bacteria. Further JTTZF-FMT induced weight loss and metabolic benefits in DIO mice, verifying that gut microbiota played a crucial role in the anti-obesity effect of JTTZF. Additionally, enrichment analysis of differential metabolites revealed that JTTZF obviously upregulated bile acid metabolism pathway, which promoted TGR5-mediated thermogenesis and energy expenditure in adipose tissue.

CONCLUSION

JTTZF exerted significant anti-obesity effect and metabolic benefits via gut-liver-adipose axis, indicating that JTTZF hold a promising potential at the preclinical stage for obesity treatment.