title: Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota.
abstract: 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.
authors.affiliation: 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.
authors.forename: Lucie
authors.initials: L
authors.lastname: Geurts
authors.affiliation: 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.
authors.forename: Amandine
authors.initials: A
authors.lastname: Everard
authors.affiliation: 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.
authors.forename: Matthias
authors.initials: M
authors.lastname: Van Hul
authors.affiliation: de Duve Institute, Université catholique de Louvain, Avenue Hippocrate, 74 B1.74.05, 1200 Brussels, Belgium.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Essaghir
authors.affiliation: 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.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Duparc
authors.affiliation: 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.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Matamoros
authors.affiliation: 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.
authors.forename: Hubert
authors.initials: H
authors.lastname: Plovier
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, UMR8251, CNRS, F-75205 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Castel
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, UMR8251, CNRS, F-75205 Paris, France.
authors.forename: Raphael G P
authors.initials: RG
authors.lastname: Denis
authors.affiliation: 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.
authors.forename: Marie
authors.initials: M
authors.lastname: Bergiers
authors.affiliation: 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.
authors.forename: Céline
authors.initials: C
authors.lastname: Druart
authors.affiliation: Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Avenue E. Mounier, 72 B1.72.11, 1200 Brussels, Belgium.
authors.forename: Mireille
authors.initials: M
authors.lastname: Alhouayek
authors.affiliation: 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.
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
authors.affiliation: Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Avenue E. Mounier, 72 B1.72.11, 1200 Brussels, Belgium.
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.affiliation: de Duve Institute, Université catholique de Louvain, Avenue Hippocrate, 74 B1.74.05, 1200 Brussels, Belgium.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Demoulin
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA, UMR8251, CNRS, F-75205 Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Luquet
authors.affiliation: 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.
authors.forename: Patrice D
authors.identifier: 0000000320402448
authors.initials: PD
authors.lastname: Cani
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology; D000818:Animals; D050218:Body Fat Distribution; D003080:Cold Temperature; D063388:Endocannabinoids / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D015870:Gene Expression; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D007249:Inflammation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D010739:Phospholipase D / Q000172:deficiency / Q000235:genetics*
chemical_list: D063388:Endocannabinoids; D010739:Phospholipase D; C506062:Napepld protein, mouse