Shuang Liu, Haifang Li, Rui Li, Yaxin Chang, Senlin Wang, Zhengang Wang, Yawen Sun, Mengying Li, Min Liu, Yunlei Zhou, Hongchao Jiao, Xiaojuan Wang, Jingpeng Zhao, Bin Li, Tongtong Zhang, Zhonghui Feng, Junbo Xu, Hai Lin
Prevotella is a poorly understood symbiont within the gut microbiota, and its role in host health remains unclear. Here, we report a case-control analysis of a Chinese cohort, in which patients with obesity showed significantly lower fecal Prevotella copri abundance. The administration of P. copri can alleviate fat deposition and promote browning in inguinal white adipose tissue (iWAT) of mice with high-fat diet (HFD)-induced adiposity. We identify succinate as a key metabolite that activates succinate receptor 1 (SUCNR1) to mimic the effects of P. copri. Mice treated with either P. copri or succinate have increased iWAT-resident macrophage populations and IL-6-STAT3 pathway activation. Forkhead box M1 (FOXM1) directly upregulates IL-6 to activate IL-6-STAT3 signaling in P. copri- or succinate-induced iWAT browning. In human WAT, we identify that P. copri and succinate levels are positively correlated with TBX1 and UCP1 transcription. This study reveals the function of P. copri in promoting iWAT browning and suggests potential strategies for alleviating adiposity and associated disorders. The gut microbiome can regulate diverse host metabolic processes, including thermogenesis in adipose tissues. Here, the authors report a reduced abundance of Prevotella copri in patients with obesity and its role in alleviating adiposity.