title: The transcriptional coactivator peroxisome proliferator activated receptor (PPAR)gamma coactivator-1 alpha and the nuclear receptor PPAR alpha control the expression of glycerol kinase and metabolism genes independently of PPAR gamma activation in human white adipocytes.
abstract: OBJECTIVE
  The purpose of this work was to determine the pattern of genes regulated by peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1 alpha (PGC-1 alpha) in human adipocytes and the involvement of PPARalpha and PPARgamma in PGC-1 alpha transcriptional action.
  
  
  METHODS
  Primary cultures of human adipocytes were transduced with a PGC-1 alpha adenovirus and treated with PPARgamma and PPARalpha agonists. Variation in gene expression was assessed using pangenomic microarrays and quantitative RT-PCR. To investigate glycerol kinase (GyK), a target of PGC-1 alpha, we measured enzymatic activity and glycerol incorporation into triglycerides. In vivo studies were performed on wild-type and PPARalpha(-/-) mice. The GyK promoter was studied using chromatin immunoprecipitation and promoter reporter gene assays.
  
  
  RESULTS
  Among the large number of genes regulated by PGC-1 alpha independently of PPARgamma, new targets involved in metabolism included the gene encoding GyK. The induction of GyK by PGC-1 alpha was observed at the levels of mRNA, enzymatic activity, and glycerol incorporation into triglycerides. PPARalpha was also upregulated by PGC-1 alpha. Its activation led to an increase in GyK expression and activity. PPARalpha was shown to bind and activate the GyK promoter. Experiments in mice confirmed the role of PGC-1 alpha and PPARalpha in the regulation of GyK in vivo.
  
  
  CONCLUSIONS
  This work uncovers novel pathways regulated by PGC-1 alpha and reveals that PPARalpha controls gene expression in human white adipocytes. The induction of GyK by PGC-1 alpha and PPARalpha may promote a futile cycle of triglyceride hydrolysis and fatty acid reesterification.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U858, Obesity Research Laboratory, Toulouse, F-31432, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Mazzucotelli
authors.forename: Nathalie
authors.initials: N
authors.lastname: Viguerie
authors.forename: Claire
authors.initials: C
authors.lastname: Tiraby
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Annicotte
authors.forename: Aline
authors.initials: A
authors.lastname: Mairal
authors.forename: Eva
authors.initials: E
authors.lastname: Klimcakova
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lepin
authors.forename: Paul
authors.initials: P
authors.lastname: Delmar
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dejean
authors.forename: Geneviève
authors.initials: G
authors.lastname: Tavernier
authors.forename: Corinne
authors.initials: C
authors.lastname: Lefort
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
authors.forename: Thierry
authors.initials: T
authors.lastname: Pineau
authors.forename: Lluis
authors.initials: L
authors.lastname: Fajas
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D005991:Glycerol Kinase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D056918:Nuclear Receptor Coactivators; D047493:PPAR alpha / Q000235:genetics* / Q000502:physiology; D047495:PPAR gamma / Q000235:genetics* / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C486559:NCOA6 protein, human; D056918:Nuclear Receptor Coactivators; D047493:PPAR alpha; D047495:PPAR gamma; D005991:Glycerol Kinase