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Nat Commun. 2015 Mar 11;6:6495. doi: 10.1038/ncomms7495.

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

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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.
de Duve Institute, Université catholique de Louvain, Avenue Hippocrate, 74 B1.74.05, 1200 Brussels, Belgium.
Université Paris Diderot, Sorbonne Paris Cité, BFA, UMR8251, CNRS, F-75205 Paris, France.
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.


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.

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