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.

Détails

ID Serval
serval:BIB_848732B2646F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
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.
Périodique
Diabetes
Auteur(s)
Mazzucotelli A., Viguerie N., Tiraby C., Annicotte J.S., Mairal A., Klimcakova E., Lepin E., Delmar P., Dejean S., Tavernier G., Lefort C., Hidalgo J., Pineau T., Fajas L., Clément K., Langin D.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Statut éditorial
Publié
Date de publication
2007
Volume
56
Numéro
10
Pages
2467-2475
Langue
anglais
Résumé
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.
RESEARCH DESIGN AND 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.
Mots-clé
Adipocytes/physiology, Gene Expression Regulation, Gene Expression Regulation, Enzymologic, Glycerol Kinase/genetics, Glycerol Kinase/metabolism, Humans, Intracellular Signaling Peptides and Proteins/metabolism, Nuclear Receptor Coactivators, PPAR alpha/genetics, PPAR alpha/physiology, PPAR gamma/genetics, PPAR gamma/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/03/2013 17:01
Dernière modification de la notice
08/05/2019 21:20
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