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

Nat Commun. 2015 Mar 11;6:6495. doi: 10.1038/ncomms7495.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, Brown / pathology
  • Adipose Tissue, White / metabolism
  • Adipose Tissue, White / pathology
  • Animals
  • Body Fat Distribution
  • Cold Temperature
  • Endocannabinoids / metabolism
  • Energy Metabolism / physiology
  • Gastrointestinal Microbiome / physiology*
  • Gene Expression
  • Glucose Intolerance / genetics
  • Glucose Intolerance / metabolism*
  • Glucose Intolerance / microbiology
  • Glucose Intolerance / pathology
  • Inflammation
  • Male
  • Mice
  • Mice, Knockout
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / microbiology
  • Obesity / pathology
  • Phospholipase D / deficiency
  • Phospholipase D / genetics*

Substances

  • Endocannabinoids
  • N-acylphosphatidylethanolamine phospholipase D, mouse
  • Phospholipase D