Lymphotoxin regulates commensal responses to enable diet-induced obesity
- 26 August 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 13 (10), 947-953
- https://doi.org/10.1038/ni.2403
Abstract
Innate immune responses influence the composition of gut microbiota. Fu and colleagues show that weight gain incurred with high-fat diets is dependent on intact lymphotoxin signaling that regulates IL-23 and IL-22 production. Microbiota are essential for weight gain in mouse models of diet-induced obesity (DIO), but the pathways that cause the microbiota to induce weight gain are unknown. We report that mice deficient in lymphotoxin, a key molecule in gut immunity, were resistant to DIO. Ltbr−/− mice had different microbial community composition compared to their heterozygous littermates, including an overgrowth of segmented filamentous bacteria (SFB). Furthermore, cecal transplantation conferred leanness to germ-free recipients. Housing Ltbr−/− mice with their obese siblings rescued weight gain in Ltbr−/− mice, demonstrating the communicability of the obese phenotype. Ltbr−/− mice lacked interleukin 23 (IL-23) and IL-22, which can regulate SFB. Mice deficient in these pathways also resisted DIO, demonstrating that intact mucosal immunity guides diet-induced changes to the microbiota to enable obesity.Keywords
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