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dc.contributor.authorBorg, ML
dc.contributor.authorAndrews, ZB
dc.contributor.authorDuh, EJ
dc.contributor.authorZechner, R
dc.contributor.authorMeikle, PJ
dc.contributor.authorWatt, MJ
dc.date.accessioned2021-02-04T01:04:01Z
dc.date.available2021-02-04T01:04:01Z
dc.date.issued2011-05-01
dc.identifierpii: db10-0845
dc.identifier.citationBorg, M. L., Andrews, Z. B., Duh, E. J., Zechner, R., Meikle, P. J. & Watt, M. J. (2011). Pigment Epithelium-Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase. DIABETES, 60 (5), pp.1458-1466. https://doi.org/10.2337/db10-0845.
dc.identifier.issn0012-1797
dc.identifier.urihttp://hdl.handle.net/11343/259255
dc.description.abstractOBJECTIVE: Pigment epithelium-derived factor (PEDF) is an adipocyte-secreted factor involved in the development of insulin resistance in obesity. Previous studies have identified PEDF as a regulator of triacylglycerol metabolism in the liver that may act through adipose triglyceride lipase (ATGL). We used ATGL(-/-) mice to determine the role of PEDF in regulating lipid and glucose metabolism. RESEARCH DESIGN AND METHODS: Recombinant PEDF was administered to ATGL(-/-) and wild-type mice, and whole-body energy metabolism was studied by indirect calorimetry. Adipose tissue lipolysis and skeletal muscle fatty acid metabolism was determined in isolated tissue preparations. Muscle lipids were assessed by electrospray ionization-tandem mass spectrometry. Whole-body insulin sensitivity and skeletal muscle glucose uptake were assessed. RESULTS: PEDF impaired the capacity to adjust substrate selection, resulting in a delayed diurnal decline in the respiratory exchange ratio, and suppressed daily fatty acid oxidation. PEDF enhanced adipocyte lipolysis and triacylglycerol lipase activity in skeletal muscle. Muscle fatty acid uptake and storage were unaffected, whereas fatty acid oxidation was impaired. These changes in lipid metabolism were abrogated in ATGL(-/-) mice and were not attributable to hypothalamic actions. ATGL(-/-) mice were also refractory to PEDF-mediated insulin resistance, but this was not related to changes in lipid species in skeletal muscle. CONCLUSIONS: The results are the first direct demonstration that 1) PEDF influences systemic fatty acid metabolism by promoting lipolysis in an ATGL-dependent manner and reducing fatty acid oxidation and 2) ATGL is required for the negative effects of PEDF on insulin action.
dc.languageEnglish
dc.publisherAMER DIABETES ASSOC
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titlePigment Epithelium-Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase
dc.typeJournal Article
dc.identifier.doi10.2337/db10-0845
melbourne.affiliation.departmentBio21
melbourne.affiliation.departmentPhysiology
melbourne.affiliation.facultyAffiliate
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleDiabetes
melbourne.source.volume60
melbourne.source.issue5
melbourne.source.pages1458-1466
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1208076
melbourne.contributor.authorMeikle, Peter
melbourne.contributor.authorWatt, Matthew
dc.identifier.eissn1939-327X
melbourne.accessrightsOpen Access


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