Dataset Information

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

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.

SUBMITTER: Everard A

PROVIDER: S-EPMC6349942 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Everard Amandine A Plovier Hubert H Rastelli Marialetizia M Van Hul Matthias M de Wouters d'Oplinter Alice A Geurts Lucie L Druart Céline C Robine Sylvie S Delzenne Nathalie M NM Muccioli Giulio G GG de Vos Willem M WM Luquet Serge S Flamand Nicolas N Di Marzo Vincenzo V Cani Patrice D PD

Nature communications 20190128 1

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<sup>∆IEC</sup>). We discovered that Napepld<sup>∆IEC</sup> mice are hyperphagic upon first high-fat diet (HFD) exposure, and develop exacerbat ...[more]

PMID: 30692526

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Dataset Information

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

Publications

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

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