PLoS ONE (Jan 2020)

ABHD11, a new diacylglycerol lipase involved in weight gain regulation.

  • Johanna Escoubet,
  • Mireille Kenigsberg,
  • Murielle Derock,
  • Veeranagouda Yaligara,
  • Marie-Dominique Bock,
  • Sandrine Roche,
  • Florence Massey,
  • Hélène de Foucauld,
  • Charles Bettembourg,
  • Anne Olivier,
  • Antoine Berthemy,
  • Joël Capdevielle,
  • Richard Legoux,
  • Eric Perret,
  • Armelle Buzy,
  • Pascale Chardenot,
  • Valérie Destelle,
  • Aurélie Leroy,
  • Christophe Cahours,
  • Sandrine Teixeira,
  • Patrick Juvet,
  • Pascal Gauthier,
  • Michaël Leguet,
  • Laurence Rocheteau-Beaujouan,
  • Marie-Agnès Chatoux,
  • Willy Deshayes,
  • Margerie Clement,
  • Mostafa Kabiri,
  • Cécile Orsini,
  • Vincent Mikol,
  • Michel Didier,
  • Jean-Claude Guillemot

DOI
https://doi.org/10.1371/journal.pone.0234780
Journal volume & issue
Vol. 15, no. 6
p. e0234780

Abstract

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Obesity epidemic continues to spread and obesity rates are increasing in the world. In addition to public health effort to reduce obesity, there is a need to better understand the underlying biology to enable more effective treatment and the discovery of new pharmacological agents. Abhydrolase domain-containing protein 11 (ABHD11) is a serine hydrolase enzyme, localized in mitochondria, that can synthesize the endocannabinoid 2-arachidonoyl glycerol (2AG) in vitro. In vivo preclinical studies demonstrated that knock-out ABHD11 mice have a similar 2AG level as WT mice and exhibit a lean metabolic phenotype. Such mice resist to weight gain in Diet Induced Obesity studies (DIO) and display normal biochemical plasma parameters. Metabolic and transcriptomic analyses on serum and tissues of ABHD11 KO mice from DIO studies show a modulation in bile salts associated with reduced fat intestinal absorption. These data suggest that modulating ABHD11 signaling pathway could be of therapeutic value for the treatment of metabolic disorders.