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Nat Commun. 2019 Jan 28;10(1):457. doi: 10.1038/s41467-018-08051-7.

Intestinal epithelial N-acylphosphatidylethanolamine phospholipase D links dietary fat to metabolic adaptations in obesity and steatosis.

Author information

1
Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life sciences and BIOtechnology (WELBIO), UCLouvain, Université catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200, Bruxelles, Belgium.
2
Institut Curie, CNRS, Unité 144, 75248, Paris, France.
3
Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, 1200, Bruxelles, Belgium.
4
Laboratory of Microbiology, Wageningen University, 6708WE, Wageningen, the Netherlands.
5
Université Paris Diderot, Sorbonne Paris Cité, BFA, UMR8251, CNRS, 75013, Paris, France.
6
Quebec Heart and Lung Institute Research Centre, Université Laval, G1V 0A6 Quebec City, Canada.
7
Institute of Nutrition and Functional Foods, Université Laval, G1V 0A6 Quebec City, Canada.
8
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Napoli, Italy.
9
Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life sciences and BIOtechnology (WELBIO), UCLouvain, Université catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200, Bruxelles, Belgium. patrice.cani@uclouvain.be.

Abstract

Variations in N-acylethanolamines (NAE) levels are associated with obesity and metabolic comorbidities. Their role in the gut remains unclear. Therefore, we generated a mouse model of inducible intestinal epithelial cell (IEC)-specific deletion of N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD), a key enzyme involved in NAE biosynthesis (Napepld∆IEC). We discovered that Napepld∆IEC mice are hyperphagic upon first high-fat diet (HFD) exposure, and develop exacerbated obesity and steatosis. These mice display hypothalamic Pomc neurons dysfunctions and alterations in intestinal and plasma NAE and 2-acylglycerols. After long-term HFD, Napepld∆IEC mice present reduced energy expenditure. The increased steatosis is associated with higher gut and liver lipid absorption. Napepld∆IEC mice display altered gut microbiota. Akkermansia muciniphila administration partly counteracts the IEC NAPE-PLD deletion effects. In conclusion, intestinal NAPE-PLD is a key sensor in nutritional adaptation to fat intake, gut-to-brain axis and energy homeostasis and thereby constitutes a novel target to tackle obesity and related disorders.

PMID:
30692526
PMCID:
PMC6349942
DOI:
10.1038/s41467-018-08051-7
[Indexed for MEDLINE]
Free PMC Article

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