The gut microbiota regulates white adipose tissue inflammation and obesity via a family of microRNAs

Abstract

The gut microbiota is a key environmental determinant of mammalian metabolism. Regulation of white adipose tissue (WAT) by the gut microbiota is a process critical to maintaining metabolic fitness, and gut dysbiosis can contribute to the development of obesity and insulin resistance (IR). However, how the gut microbiota regulates WAT function remains largely unknown. Here, we show that tryptophan-derived metabolites produced by the gut microbiota controlled the expression of the <i>miR-181</i> family in white adipocytes in mice to regulate energy expenditure and insulin sensitivity. Moreover, dysregulation of the gut microbiota-<i>miR-181</i> axis was required for the development of obesity, IR, and WAT inflammation in mice. Our results indicate that regulation of <i>miR-181</i> in WAT by gut microbiota-derived metabolites is a central mechanism by which host metabolism is tuned in response to dietary and environmental changes. As we also found that <i>MIR-181</i> expression in WAT and the plasma abundance of tryptophan-derived metabolites were dysregulated in a cohort of obese human children, the <i>MIR-181</i> family may represent a potential therapeutic target to modulate WAT function in the context of obesity.