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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.

Author information

1
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.
2
de Duve Institute, Université catholique de Louvain, Avenue Hippocrate, 74 B1.74.05, 1200 Brussels, Belgium.
3
Université Paris Diderot, Sorbonne Paris Cité, BFA, UMR8251, CNRS, F-75205 Paris, France.
4
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.

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.

PMID:
25757720
PMCID:
PMC4382707
DOI:
10.1038/ncomms7495
[Indexed for MEDLINE]
Free PMC Article

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