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

Author

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, and Jean-Claude Guillemot

Subjects
Medicine, Science
Abstract

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.

Published
2020
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2. ABHD11, a new diacylglycerol lipase involved in weight gain regulation

Author

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

Subjects
0301 basic medicine, Diacylglycerol lipase, Physiology, Hydrolases, medicine.medical_treatment, Weight Gain, Biochemistry, Intestinal absorption, Feces, Gene Knockout Techniques, Mice, 0302 clinical medicine, Endocrinology, Mathematical and Statistical Techniques, Medicine and Health Sciences, Bile, Insulin, Lipases, Energy-Producing Organelles, Multidisciplinary, biology, Statistics, Serine hydrolase, Genomics, Endocannabinoid system, Lipids, Mitochondria, Body Fluids, Enzymes, Physical Sciences, MCF-7 Cells, Medicine, Signal transduction, Cellular Structures and Organelles, Anatomy, Transcriptome Analysis, Signal Transduction, Research Article, medicine.medical_specialty, Science, Bioenergetics, Research and Analysis Methods, Gene Expression Regulation, Enzymologic, 03 medical and health sciences, In vivo, Internal medicine, medicine, Genetics, Animals, Humans, Statistical Methods, Nutrition, Diabetic Endocrinology, Analysis of Variance, Gene Expression Profiling, Biology and Life Sciences, Proteins, Computational Biology, Cell Biology, Genome Analysis, In vitro, Hormones, Diet, 030104 developmental biology, biology.protein, Enzymology, Serine Proteases, 030217 neurology & neurosurgery, Mathematics
Abstract

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.

Published
2020

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