• Lucie Geurts, Amandine Everard, Matthias Van Hul, Ahmed Essaghir, Thibaut Duparc, Sébastien Matamoros, Hubert Plovier, Julien Castel, Raphael G P Denis, Marie Bergiers, Céline Druart, Mireille Alhouayek, Nathalie M Delzenne, Giulio G Muccioli, Jean-Baptiste Demoulin, Serge Luquet, and Patrice D Cani.
• Metabolism and Nutrition Research Group, WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Université catholique de Louvain, Avenue E. Mounier, 73 B1.73.11, 1200 Brussels, Belgium.
• Nat Commun. 2015 Jan 1;6:6495.

AbstractObesity is a pandemic disease associated with many metabolic alterations and involves several organs and systems. The endocannabinoid system (ECS) appears to be a key regulator of energy homeostasis and metabolism. Here we show that specific deletion of the ECS synthesizing enzyme, NAPE-PLD, in adipocytes induces obesity, glucose intolerance, adipose tissue inflammation and altered lipid metabolism. We report that Napepld-deleted mice present an altered browning programme and are less responsive to cold-induced browning, highlighting the essential role of NAPE-PLD in regulating energy homeostasis and metabolism in the physiological state. Our results indicate that these alterations are mediated by a shift in gut microbiota composition that can partially transfer the phenotype to germ-free mice. Together, our findings uncover a role of adipose tissue NAPE-PLD on whole-body metabolism and provide support for targeting NAPE-PLD-derived bioactive lipids to treat obesity and related metabolic disorders.

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