Polymerase I and transcript release factor regulates lipolysis via a phosphorylation-dependent mechanism.

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 adipo...

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Publicado en:Diabetes Vol. 60; no. 3; pp. 757 - 766
Autores principales: Aboulaich N, Chui PC, Asara JM, Flier JS, Maratos-Flier E, Aboulaich, Nabila, Chui, Patricia C, Asara, John M, Flier, Jeffrey S, Maratos-Flier, Eleftheria
Formato: research Journal Article
Publicado: American Diabetes Association Mar2011
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Mar2011
      vid: 60
      iid: 3
      pid: 1367
      pub: American Diabetes Association
      place: Arlington, Virginia
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        104834782
        NLM21282370
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        10.2337/db10-0744
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        104834782
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        atl: Polymerase I and transcript release factor regulates lipolysis via a phosphorylation-dependent mechanism.
      aug:
        au:
          Aboulaich N
          Chui PC
          Asara JM
          Flier JS
          Maratos-Flier E
          Aboulaich, Nabila
          Chui, Patricia C
          Asara, John M
          Flier, Jeffrey S
          Maratos-Flier, Eleftheria
        affil: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
      sug:
        subj:
          Adipocytes Metabolism
          Adipose Tissue Metabolism
          Lipid Metabolism, Inborn Errors
          Proteins Metabolism
          Adipocytes
          Adipocytes Drug Effects
          Adipose Tissue Drug Effects
          Adrenergic beta-Agonists Pharmacodynamics
          Animal Studies
          Blotting, Western
          Cells
          Chromatography, Liquid
          Immunity
          Insulin Pharmacodynamics
          Isoproterenol Pharmacodynamics
          Mass Spectrometry
          Metabolism Drug Effects
          Metabolism Physiology
          Mice
          Proteins
          Reverse Transcriptase Polymerase Chain Reaction
          RNA
          RNA Metabolism
      ab: 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.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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