Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota

• Published in: Nature communications Vol. 6; no. 1; p. 6495
• Main Authors: Geurts, Lucie, Everard, Amandine, Van Hul, Matthias, Essaghir, Ahmed, Duparc, Thibaut, Matamoros, Sébastien, Plovier, Hubert, Castel, Julien, Denis, Raphael G. P., Bergiers, Marie, Druart, Céline, Alhouayek, Mireille, Delzenne, Nathalie M., Muccioli, Giulio G., Demoulin, Jean-Baptiste, Luquet, Serge, Cani, Patrice D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.03.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 631/443/319/1642/393; 631/443/319/2723; 692/308; 692/698/2741/2135; Adipocytes; Adipose Tissue, Brown - metabolism; Adipose Tissue, Brown - pathology; Adipose Tissue, White - metabolism; Adipose Tissue, White - pathology; Animals; Body fat; Body Fat Distribution; Cold Temperature; Diet; Endocannabinoids - metabolism; Energy; Energy Metabolism - physiology; Enzymes; Gastrointestinal Microbiome - physiology; Gene Expression; Glucose Intolerance - genetics; Glucose Intolerance - metabolism; Glucose Intolerance - microbiology; Glucose Intolerance - pathology; Homeostasis; Humanities and Social Sciences; Inflammation; Lipids; Male; Metabolism; Mice; Mice, Knockout; Microbiota; multidisciplinary; Nutrition research; Obesity; Obesity - genetics; Obesity - metabolism; Obesity - microbiology; Obesity - pathology; Pandemics; Phospholipase D - deficiency; Phospholipase D - genetics; Physiology; Science; Science (multidisciplinary); Belgium
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms7495

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. Endocannabinoids are bioactive lipid molecules produced in the body. Here, Geurts et al . create mice lacking the endocannabinoid-producing enzyme NAPE-PLD in adipocytes and report defects in adipose-induced browning, which are mediated by alterations in the gut microbiome.