The microbiota regulates white adipose tissue inflammation and progression of obesity through a highly conserved family of microRNAs.

The gut microbiota is a key environmental determinant of mammalian metabolism. Regulation of white adipose tissue (WAT) by the gut microbiota is a critical process that maintains metabolic fitness, while dysbiosis contributes to the development of obesity and insulin resistance (IR). However, how the gut microbiota controls WAT functions remain largely unknown. Herein, we show that tryptophan-derived metabolites produced by the microbiota control the expression of the miR-181 family in white adipocytes to regulate energy expenditure and insulin sensitivity. Moreover, we show that dysregulation of the microbiota-miR-181 axis is required for the development of obesity, IR, and WAT inflammation. Thus, our results indicate that regulation of miRNA levels in WAT by microbiota-derived cues is a central mechanism by which host metabolism is tuned in response to dietary and environmental changes. As MIR-181 is dysregulated in WAT from obese human individuals, the MIR-181 family may represent a potential therapeutic target to modulate WAT function in the context of obesity. Epididymal white adipose tissue (eWAT) mRNA profiles of wild type (WT) and miR-181-double knockout mice following 12 weeks on high fat diet.