| Monoglyceride lipase deficiency in mice impairs lipolysis and attenuates diet-induced insulin resistance. | |
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MedLine Citation:
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PMID: 21454566 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Monoglyceride lipase (MGL) influences energy metabolism by at least two mechanisms. First, it hydrolyzes monoacylglycerols (MG) into fatty acids and glycerol. These products can be used for energy production or synthetic reactions. Second, MGL degrades 2-arachidonoyl glycerol (2-AG), the most abundant endogenous ligand of cannabinoid receptors (CBR). Activation of CBR affects energy homeostasis by central orexigenic stimuli, by promoting lipid storage, and by reducing energy expenditure. To characterize the metabolic role of MGL in vivo, we generated an MGL-deficient mouse model (MGL-ko). These mice exhibit a reduction in MG hydrolase activity and a concomitant increase in MG levels in adipose tissue, brain, and liver. In adipose tissue, the lack of MGL activity is partially compensated by hormone-sensitive lipase. Nonetheless, fasted MGL-ko mice exhibit reduced plasma glycerol and triacylglycerol, as well as liver triacylglycerol levels indicative for impaired lipolysis. Despite a strong elevation of 2-AG levels, MGL-ko mice exhibit normal food intake, fat mass, and energy expenditure. Yet mice lacking MGL show a pharmacological tolerance to the CBR agonist CP 55,940 suggesting that the elevated 2-AG levels are functionally antagonized by desensitization of CBR. Interestingly, however, MGL-ko mice receiving a high fat diet exhibit significantly improved glucose tolerance and insulin sensitivity in comparison with wild-type controls despite equal weight gain. In conclusion, our observations implicate that MGL deficiency impairs lipolysis and attenuates diet-induced insulin resistance. Defective degradation of 2-AG does not provoke cannabinoid-like effects on feeding behavior, lipid storage, and energy expenditure, which may be explained by desensitization of CBR. |
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Authors:
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Ulrike Taschler; Franz P W Radner; Christoph Heier; Renate Schreiber; Martina Schweiger; Gabriele Schoiswohl; Karina Preiss-Landl; Doris Jaeger; Birgit Reiter; Harald C Koefeler; Jacek Wojciechowski; Christian Theussl; Josef M Penninger; Achim Lass; Guenter Haemmerle; Rudolf Zechner; Robert Zimmermann |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-03-23 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-16 Completed Date: 2011-07-26 Revised Date: 2012-05-22 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 17467-77 Citation Subset: IM |
Copyright Information:
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© 2011 by The American Society for Biochemistry and Molecular Biology, Inc. |
Affiliation:
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Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipose Tissue
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enzymology*,
metabolism Animals Arachidonic Acids / genetics, metabolism Diet* Energy Metabolism / physiology Feeding Behavior / physiology Glycerides / genetics, metabolism Glycerol / blood Insulin Resistance* Lipolysis / physiology* Mice Mice, Knockout Monoacylglycerol Lipases / genetics, metabolism* Receptors, Cannabinoid / genetics, metabolism Triglycerides / blood, genetics |
| Grant Support | |
ID/Acronym/Agency:
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P 21296-B19//Austrian Science Fund FWF |
| Chemical | |
Reg. No./Substance:
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0/Arachidonic Acids; 0/Glycerides; 0/Receptors, Cannabinoid; 0/Triglycerides; 53847-30-6/2-arachidonylglycerol; 56-81-5/Glycerol; EC 3.1.1.23/Monoacylglycerol Lipases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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