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

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  • Lucie Geurts

    (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)

  • Amandine Everard

    (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)

  • Matthias Van Hul

    (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)

  • Ahmed Essaghir

    (de Duve Institute, Université catholique de Louvain, Avenue Hippocrate, 74 B1.74.05, 1200 Brussels, Belgium)

  • Thibaut Duparc

    (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)

  • Sébastien Matamoros

    (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)

  • Hubert Plovier

    (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)

  • Julien Castel

    (Université Paris Diderot, Sorbonne Paris Cité, BFA)

  • Raphael G. P. Denis

    (Université Paris Diderot, Sorbonne Paris Cité, BFA)

  • Marie Bergiers

    (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)

  • Céline Druart

    (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)

  • Mireille Alhouayek

    (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)

  • Nathalie M. Delzenne

    (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)

  • Giulio G. Muccioli

    (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)

  • Jean-Baptiste Demoulin

    (de Duve Institute, Université catholique de Louvain, Avenue Hippocrate, 74 B1.74.05, 1200 Brussels, Belgium)

  • Serge Luquet

    (Université Paris Diderot, Sorbonne Paris Cité, BFA)

  • Patrice D. Cani

    (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)

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.

Suggested Citation

  • 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 & Mir, 2015. "Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota," Nature Communications, Nature, vol. 6(1), pages 1-15, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7495
    DOI: 10.1038/ncomms7495
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