title: Global deletion of MGL in mice delays lipid absorption and alters energy homeostasis and diet-induced obesity.
abstract: Monoacylglycerol lipase (MGL) is a ubiquitously expressed enzyme that catalyzes the hydrolysis of monoacylglycerols (MGs) to yield FFAs and glycerol. MGL contributes to energy homeostasis through the mobilization of fat stores and also via the degradation of the endocannabinoid 2-arachidonoyl glycerol. To further examine the role of MG metabolism in energy homeostasis, MGL(-/-) mice were fed either a 10% (kilocalories) low-fat diet (LFD) or a 45% (kilocalories) high-fat diet (HFD) for 12 weeks. Profound increases of MG species in the MGL(-/-) mice compared with WT control mice were found. Weight gain over the 12 weeks was blunted in both diet groups. MGL(-/-) mice were leaner than WT mice at both baseline and after 12 weeks of LFD feeding. Circulating lipids were decreased in HFD-fed MGL(-/-) mice, as were the levels of several plasma peptides involved in glucose homeostasis and energy balance. Interestingly, MGL(-/-) mice had markedly reduced intestinal TG secretion following an oral fat challenge, suggesting delayed lipid absorption. Overall, the results indicate that global MGL deletion leads to systemic changes that produce a leaner phenotype and an improved serum metabolic profile.
authors.affiliation: Department of Nutritional Sciences Rutgers University, New Brunswick, NJ 08901.
authors.forename: John D
authors.initials: JD
authors.lastname: Douglass
authors.affiliation: Department of Nutritional Sciences Rutgers University, New Brunswick, NJ 08901.
authors.forename: Yin Xiu
authors.initials: YX
authors.lastname: Zhou
authors.affiliation: Department of Nutritional Sciences Rutgers University, New Brunswick, NJ 08901.
authors.forename: Amy
authors.initials: A
authors.lastname: Wu
authors.affiliation: Department of Nutritional Sciences Rutgers University, New Brunswick, NJ 08901.
authors.forename: John A
authors.initials: JA
authors.lastname: Zadroga
authors.affiliation: Department of Nutritional Sciences Rutgers University, New Brunswick, NJ 08901.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gajda
authors.affiliation: Department of Nutritional Sciences Rutgers University, New Brunswick, NJ 08901.
authors.forename: Atreju I
authors.initials: AI
authors.lastname: Lackey
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA 19477.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Lang
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA 19477.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Chevalier
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA 19477.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Sutton
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA 19477.
authors.forename: Sui-Po
authors.initials: SP
authors.lastname: Zhang
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA 19477.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Flores
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA 19477.
authors.forename: Margery A
authors.initials: MA
authors.lastname: Connelly
authors.affiliation: Department of Nutritional Sciences Rutgers University, New Brunswick, NJ 08901 Rutgers Center for Lipid Research, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ 08901.
authors.forename: Judith
authors.initials: J
authors.lastname: Storch
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000097:blood*; D063388:Endocannabinoids / Q000097:blood; D004734:Energy Metabolism / Q000235:genetics*; D006706:Homeostasis; D008055:Lipids / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D008994:Monoacylglycerol Lipases / Q000097:blood* / Q000235:genetics; D050178:Monoglycerides / Q000097:blood; D009765:Obesity / Q000097:blood* / Q000235:genetics / Q000473:pathology; D015430:Weight Gain / Q000235:genetics*
chemical_list: D004041:Dietary Fats; D063388:Endocannabinoids; D008055:Lipids; D050178:Monoglycerides; D008994:Monoacylglycerol Lipases
keywords: monoacylglycerol lipase; monoacylglycerols; monoglycerides
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