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

microbiome mir-181 white adipose tissue wat microrna tryptophan

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#1 Engadin

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Posted 13 June 2019 - 09:59 PM


B E H I N D   P A Y W A L L !

 

 

S O U R C E :   Science Translational Medicine

 

 

 

A gut-fat axis

 

Whether and how the gut microbiome affects adipose tissue homeostasis is an area of current investigation. Virtue et al. showed that a high-fat diet in mice led to the activation of miR-181 in white adipose tissue (WAT) and subsequent obesity, insulin resistance, and WAT inflammation. The authors tied the increased expression of this microRNA to a reduction in circulating microbiota-derived metabolites produced by tryptophan metabolism in the gut and confirmed this link by administering indole to mice. miR-181 was increased in WAT and indole was reduced in the plasma of obese humans, suggesting the potential relevance of this axis to human disease.

 

 

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 miR-181 family in white adipocytes in mice to regulate energy expenditure and insulin sensitivity. Moreover, dysregulation of the gut microbiota–miR-181axis was required for the development of obesity, IR, and WAT inflammation in mice. Our results indicate that regulation of miR-181 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 MIR-181 expression in WAT and the plasma abundance of tryptophan-derived metabolites were dysregulated in a cohort of obese human children, the MIR-181 family may represent a potential therapeutic target to modulate WAT function in the context of obesity.

 

 

 

 


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Also tagged with one or more of these keywords: microbiome, mir-181, white adipose tissue, wat, microrna, tryptophan

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