Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status

被引：184

作者：

Everard, Amandine ^{[1
]}

Geurts, Lucie ^{[1
]}

Caesar, Robert ^{[2
,3
]}

Van Hul, Matthias ^{[1
]}

Matamoros, Sebastien ^{[1
]}

Duparc, Thibaut ^{[1
]}

Denis, Raphael G. P. ^{[4
]}

Cochez, Perrine ^{[5
]}

Pierard, Florian ^{[1
]}

Castel, Julien ^{[4
]}

Bindels, Laure B. ^{[1
]}

Plovier, Hubert ^{[1
]}

Robine, Sylvie ^{[6
]}

Muccioli, Giulio G. ^{[7
]}

Renauld, Jean-Christophe ^{[5
]}

Dumoutier, Laure ^{[5
]}

Delzenne, Nathalie M. ^{[1
]}

Luquet, Serge ^{[4
]}

Baeckhed, Fredrik ^{[2
,3
]}

Cani, Patrice D. ^{[1
]}

机构：

[1] Catholic Univ Louvain, Louvain Drug Res Inst, WELBIO Walloon Excellence Life Sci & BIOtechnol, Metab & Nutr Res Grp, B-1200 Brussels, Belgium

[2] Sahlgrens Univ Hosp, Sahlgrenska Ctr Cardiovasc & Metab Res, Wallenberg Lab, S-40530 Gothenburg, Sweden

[3] Univ Gothenburg, Dept Mol & Clin Med, S-41345 Gothenburg, Sweden

[4] Univ Paris Diderot, Sorbonne Paris Cite, BFA, UMR8251, F-75205 Paris, France

[5] Catholic Univ Louvain, Ludwig Inst Canc Res, Expt Med Unit, B-1200 Brussels, Belgium

[6] CNRS, Inst Curie, Unite Mixte Rech 144, F-75005 Paris, France

[7] Catholic Univ Louvain, Louvain Drug Res Inst, Bioanal & Pharmacol Bioact Lipids Res Grp, B-1200 Brussels, Belgium

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

欧洲研究理事会;

关键词：

DIET-INDUCED OBESITY; ALTERED GUT MICROBIOTA; T-CELL DEVELOPMENT; GENE-EXPRESSION; INNATE IMMUNITY; ADIPOSE-TISSUE; PANETH CELLS; PROTEIN; IN-VIVO; MICE;

D O I：

10.1038/ncomms6648

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Obesity is associated with a cluster of metabolic disorders, low-grade inflammation and altered gut microbiota. Whether host metabolism is controlled by intestinal innate immune system and the gut microbiota is unknown. Here we report that inducible intestinal epithelial cell-specific deletion of MyD88 partially protects against diet-induced obesity, diabetes and inflammation. This is associated with increased energy expenditure, an improved glucose homeostasis, reduced hepatic steatosis, fat mass and inflammation. Protection is transferred following gut microbiota transplantation to germ-free recipients. We also demonstrate that intestinal epithelial MyD88 deletion increases anti-inflammatory endocannabinoids, restores antimicrobial peptides production and increases intestinal regulatory T cells during diet-induced obesity. Targeting MyD88 after the onset of obesity reduces fat mass and inflammation. Our work thus identifies intestinal epithelial MyD88 as a sensor changing host metabolism according to the nutritional status and we show that targeting intestinal epithelial MyD88 constitutes a putative therapeutic target for obesity and related disorders.

引用

页数：12

共 57 条

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