Polymerase I and Transcript Release Factor Regulates Lipolysis via a Phosphorylation-Dependent Mechanism

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Polymerase I and Transcript Release Factor Regulates Lipolysis via a Phosphorylation-Dependent Mechanism

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dc.contributor.author Aboulaich, Nabila
dc.contributor.author Chui, Patricia C.
dc.contributor.author Asara, John M
dc.contributor.author Flier, Jeffrey S.
dc.contributor.author Maratos-Flier, Eleftheria
dc.date.accessioned 2012-08-10T18:11:30Z
dc.date.issued 2011
dc.identifier.citation Aboulaich, Nabila, Patricia C. Chui, John M. Asara, Jeffrey S. Flier, and Eleftheria Maratos-Flier. 2011. Polymerase I and transcript release factor regulates lipolysis via a phosphorylation-dependent mechanism. Diabetes 60(3): 757-765. en_US
dc.identifier.issn 0012-1797 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:9393256
dc.description.abstract OBJECTIVE: Polymerase I and transcript release factor (PTRF) is a protein highly expressed in adipose tissue and is an integral structural component of caveolae. Here, we report on a novel role of PTRF in lipid mobilization. RESEARCH DESIGN AND METHODS: PTRF expression was examined in different adipose depots of mice during fasting, refeeding, and after administration of catecholamines and insulin. Involvement of PTRF during lipolysis was studied upon PTRF knockdown and overexpression and mutation of PTRF phosphorylation sites in 3T3-L1 adipocytes. RESULTS: PTRF expression in mouse white adipose tissue (WAT) is regulated by nutritional status, increasing during fasting and decreasing to baseline after refeeding. Expression of PTRF also is hormonally regulated because treatment of mice with insulin leads to a decrease in expression, whereas isoproterenol increases expression in WAT. Manipulation of PTRF levels revealed a role of PTRF in lipolysis. Lentiviral-mediated knockdown of PTRF resulted in a marked attenuation of glycerol release in response to isoproterenol. Conversely, overexpressing PTRF enhanced isoproterenol-stimulated glycerol release. Mass-spectrometric analysis revealed that PTRF is phosphorylated at multiple sites in WAT. Mutation of serine 42, threonine 304, or serine 368 to alanine reduced isoproterenol-stimulated glycerol release in 3T3-L1 adipocytes. CONCLUSIONS: Our study is the first direct demonstration for a novel adipose tissue–specific function of PTRF as a mediator of lipolysis and also shows that phosphorylation of PTRF is required for efficient fat mobilization. en_US
dc.language.iso en_US en_US
dc.publisher American Diabetes Association en_US
dc.relation.isversionof doi:10.2337/db10-0744 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046836/pdf/ en_US
dash.license LAA
dc.title Polymerase I and Transcript Release Factor Regulates Lipolysis via a Phosphorylation-Dependent Mechanism en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Diabetes en_US
dash.depositing.author Asara, John M
dc.date.available 2012-08-10T18:11:30Z

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