|Title||Intestinal epithelial N-acylphosphatidylethanolamine phospholipase D links dietary fat to metabolic adaptations in obesity and steatosis|
|Author(s)||Everard, Amandine; Plovier, Hubert; Rastelli, Marialetizia; Hul, Matthias Van; Wouters d’Oplinter, Alice de; Geurts, Lucie; Druart, Céline; Robine, Sylvie; Delzenne, Nathalie M.; Muccioli, Giulio G.; Vos, Willem M. de; Luquet, Serge; Flamand, Nicolas; Marzo, Vincenzo Di; Cani, Patrice D.|
|Source||Nature Communications 10 (2019)1. - ISSN 2041-1723|
|Publication type||Refereed Article in a scientific journal|
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.