| Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. | |
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MedLine Citation:
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PMID: 19723629 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Triacylglycerol accumulation in insulin target tissues is associated with insulin resistance. Paradoxically, mice with global targeted deletion of adipose triglyceride lipase (ATGL), the rate-limiting enzyme in triacylglycerol hydrolysis, display improved glucose tolerance and insulin sensitivity despite triacylglycerol accumulation in multiple tissues. To determine the molecular mechanisms for this phenotype, ATGL-deficient (ATGL(-/-)) and wild-type mice were injected with saline or insulin (10 units/kg, intraperitoneally), and then phosphorylation and activities of key insulin-signaling proteins were determined in insulin target tissues (liver, adipose tissue, and muscle). Insulin signaling and/or glucose transport was also evaluated in isolated adipocytes and skeletal muscle ex vivo. In ATGL(-/-) mice, insulin-stimulated phosphatidylinositol 3-kinase and Akt activities as well as phosphorylation of critical residues of IRS1 (Tyr(P)-612) and Akt (Ser(P)-473) were increased in skeletal muscle in vivo. Insulin-stimulated phosphatidylinositol 3-kinase activity and total insulin receptor and insulin receptor substrate 1, but not other parameters, were also increased in white adipose tissue in vivo. In contrast, in vivo measures of insulin signaling were decreased in brown adipose tissue and liver. Interestingly, the enhanced components of insulin signaling identified in skeletal muscle and white adipose tissue in vivo and their expected downstream effects on glucose transport were not present ex vivo. ATGL deficiency altered intramyocellular lipids as well as serum factors known to influence insulin sensitivity. Thus, skeletal muscle, rather than other tissues, primarily contributes to enhanced insulin sensitivity in ATGL(-/-) mice in vivo despite triacylglycerol accumulation, and both local and systemic factors contribute to tissue-specific effects of global ATGL deficiency on insulin action. |
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Authors:
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Petra C Kienesberger; Daeho Lee; Thomas Pulinilkunnil; Daniel S Brenner; Lingzhi Cai; Christoph Magnes; Harald C Koefeler; Ingo E Streith; Gerald N Rechberger; Guenter Haemmerle; Jeffrey S Flier; Rudolf Zechner; Young-Bum Kim; Erin E Kershaw |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-08-31 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 284 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-26 Completed Date: 2009-12-14 Revised Date: 2011-12-26 |
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: 30218-29 Citation Subset: IM |
Affiliation:
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From the 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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metabolism,
pathology* Animals Insulin / metabolism* Insulin Resistance Lipase / deficiency* Mice Mice, Knockout Muscle, Skeletal Signal Transduction* Tissue Distribution Triglycerides / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK043051/DK/NIDDK NIH HHS; F 3001-B19//Austrian Science Fund FWF; F 3002-B19//Austrian Science Fund FWF; K08 DK065833-06/DK/NIDDK NIH HHS; K08-DK065833/DK/NIDDK NIH HHS; P30-DK57521/DK/NIDDK NIH HHS; R03 DK077697-03/DK/NIDDK NIH HHS; R03-DK077697/DK/NIDDK NIH HHS; R37-DK028082/DK/NIDDK NIH HHS; W 901-B12//Austrian Science Fund FWF; Z 136-B05//Austrian Science Fund FWF |
| Chemical | |
Reg. No./Substance:
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0/Insulin; 0/Triglycerides; EC 3.1.1.3/Lipase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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