Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota.
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, Patrice D Cani
Obesity 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.
