title: Over-expression of monoacylglycerol lipase (MGL) in small intestine alters endocannabinoid levels and whole body energy balance, resulting in obesity.
abstract: The function of small intestinal monoacylglycerol lipase (MGL) is unknown. Its expression in this tissue is surprising because one of the primary functions of the small intestine is to convert diet-derived MGs to triacylglycerol (TG), and not to degrade them. To elucidate the function of intestinal MGL, we generated transgenic mice that over-express MGL specifically in small intestine (iMGL mice). After only 3 weeks of high fat feeding, iMGL mice showed an obese phenotype; body weight gain and body fat mass were markedly higher in iMGL mice, along with increased hepatic and plasma TG levels compared to wild type littermates. The iMGL mice were hyperphagic and displayed reduced energy expenditure despite unchanged lean body mass, suggesting that the increased adiposity was due to both increased caloric intake and systemic effects resulting in a hypometabolic rate. The presence of the transgene resulted in lower levels of most MG species in intestinal mucosa, including the endocannabinoid 2-arachidonoyl glycerol (2-AG). The results therefore suggest a role for intestinal MGL, and intestinal 2-AG and perhaps other MG species, in whole body energy balance via regulation of food intake as well as metabolic rate.
authors.affiliation: Department of Nutritional Sciences, Rutgers University, New Brunswick, New Jersey, United States of America.
authors.forename: Su-Hyoun
authors.initials: SH
authors.lastname: Chon
authors.forename: John D
authors.initials: JD
authors.lastname: Douglass
authors.forename: Yin Xiu
authors.initials: YX
authors.lastname: Zhou
authors.forename: Nashmia
authors.initials: N
authors.lastname: Malik
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Dixon
authors.forename: Anita
authors.initials: A
authors.lastname: Brinker
authors.forename: Loredana
authors.initials: L
authors.lastname: Quadro
authors.forename: Judith
authors.initials: J
authors.lastname: Storch
mesh_terms: D050154:Adiposity / Q000502:physiology; D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D001066:Appetite / Q000502:physiology; D001095:Arachidonic Acids / Q000378:metabolism*; D001481:Basal Metabolism / Q000502:physiology; D001921:Brain / Q000378:metabolism; D004435:Eating / Q000502:physiology; D063388:Endocannabinoids / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D005989:Glycerides / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008994:Monoacylglycerol Lipases / Q000235:genetics* / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D054369:Agouti-Related Protein; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D009478:Neuropeptide Y; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D014280:Triglycerides; D011333:Pro-Opiomelanocortin; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases; C078814:anandamide