The gut microbiota regulates white adipose tissue inflammation and obesity via a family of microRNAs.
Document Type
Article
Publication Date
6-12-2019
Keywords
JGM
JAX Source
Sci Transl Med 2019 Jun 12; 11(496):eaav1892
Volume
11
Issue
496
ISSN
1946-6242
PMID
31189717
DOI
https://doi.org/10.1126/scitranslmed.aav1892
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-181 axis 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.
Recommended Citation
Virtue A,
McCright S,
Wright J,
Jimenez M,
Mowel W,
Kotzin J,
Joannas L,
Basavappa M,
Spencer S,
Clark M,
Eisennagel S,
Williams A,
Levy M,
Manne S,
Henrickson S,
Wherry E,
Thaiss C,
Elinav E,
Henao-Mejia J.
The gut microbiota regulates white adipose tissue inflammation and obesity via a family of microRNAs. Sci Transl Med 2019 Jun 12; 11(496):eaav1892