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

Amandine Everard, Lucie Geurts, Robert Caesar, Matthias Van Hul, Sébastien Matamoros, Thibaut Duparc, Raphael G. P. Denis, Perrine Cochez, Florian Pierard, Julien Castel, Laure B. Bindels, Hubert Plovier, Sylvie Robine, Giulio G. Muccioli, Jean-Christophe Renauld, Laure Dumoutier, Nathalie M. Delzenne, Serge Luquet, Fredrik Bäckhed and Patrice D. Cani ()
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Amandine Everard: Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group
Lucie Geurts: Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group
Robert Caesar: Wallenberg Laboratory/Sahlgrenska Center for Cardiovascular and Metabolic Research, Sahlgrenska University Hospital
Matthias Van Hul: Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group
Sébastien Matamoros: Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group
Thibaut Duparc: Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group
Raphael G. P. Denis: Université Paris Diderot, Sorbonne Paris Cité, BFA, UMR8251, CNRS
Perrine Cochez: Université Catholique de Louvain, Ludwig Institute for Cancer Research, Experimental Medicine Unit
Florian Pierard: Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group
Julien Castel: Université Paris Diderot, Sorbonne Paris Cité, BFA, UMR8251, CNRS
Laure B. Bindels: Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group
Hubert Plovier: Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group
Sylvie Robine: Institut Curie, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 144
Giulio G. Muccioli: Université Catholique de Louvain, Louvain Drug Research Institute, Bioanalysis and Pharmacology of Bioactive Lipids Research Group
Jean-Christophe Renauld: Université Catholique de Louvain, Ludwig Institute for Cancer Research, Experimental Medicine Unit
Laure Dumoutier: Université Catholique de Louvain, Ludwig Institute for Cancer Research, Experimental Medicine Unit
Nathalie M. Delzenne: Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group
Serge Luquet: Université Paris Diderot, Sorbonne Paris Cité, BFA, UMR8251, CNRS
Fredrik Bäckhed: Wallenberg Laboratory/Sahlgrenska Center for Cardiovascular and Metabolic Research, Sahlgrenska University Hospital
Patrice D. Cani: Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms6648

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