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

TitleIntestinal epithelial N-acylphosphatidylethanolamine phospholipase D links dietary fat to metabolic adaptations in obesity and steatosis.
Publication TypeJournal Article
Year of Publication2019
AuteursEverard, A, Plovier, H, Rastelli, M, Van Hul, M, d'Oplinter, Ade Wouters, Geurts, L, Druart, C, Robine, S, Delzenne, NM, Muccioli, GG, de Vos, WM, Luquet, S, Flamand, N, Di Marzo, V, Cani, PD
JournalNat Commun
Volume10
Issue1
Pagination457
Date Published2019 01 28
ISSN2041-1723
KeywordsAdaptation, Physiological, Animals, Diet, High-Fat, Dietary Fats, Fatty Liver, Gastrointestinal Microbiome, Homeostasis, Intestinal Mucosa, Lipid Metabolism, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Obesity, Phosphatidylethanolamines, Phospholipase D
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). We discovered that Napepld 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 mice present reduced energy expenditure. The increased steatosis is associated with higher gut and liver lipid absorption. Napepld 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.

DOI10.1038/s41467-018-08051-7
Alternate JournalNat Commun
PubMed ID30692526
PubMed Central IDPMC6349942
Grant List336452 / / European Research Council / International