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Submitted on June 24, 2009
Accepted on October 9, 2009
Control of Lipid and Glucose Metabolism in Human White Adipocytes
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 858 (C.R., E.M., C.V., V.B., A.Maz., A.Mai., N.V., D.L.), Obesity Research Laboratory, and Université de Toulouse, Paul Sabatier University, Rangueil Institute of Molecular Medicine (I2MR), Institut Fédératif de Recherche 150, F-31432 Toulouse, France; and Centre Hospitalier Universitaire de Toulouse (D.L.), Biochemistry Laboratory, Biology Institute of Purpan, F-31059 Toulouse, France
* To whom correspondence should be addressed. E-mail: dominique.langin{at}inserm.fr.
This work aimed at characterizing the role of peroxisome proliferator-activated receptors (PPAR)
in human white adipocyte metabolism and at comparing PPAR
and PPAR
actions in these cells. Primary cultures of human fat cells were treated with the PPAR
agonist GW7647 or the PPAR
agonist rosiglitazone. Changes in gene expression were determined using DNA microrrays and quantitative RT-PCR. Western blot and metabolic studies were performed to identify the biological effects elicited by PPAR agonist treatments. GW7647 induced an up-regulation of
-oxidation gene expression and increased palmitate oxidation. Unexpectedly, glycolysis was strongly reduced at transcriptional and functional levels by GW7647 leading to a decrease in pyruvate and lactate production. Glucose oxidation was decreased. Triglyceride esterification and de novo lipogenesis were inhibited by the PPAR
agonist. GW7647-induced alterations were abolished by a treatment with a PPAR
antagonist. Small interfering RNA-mediated extinction of PPAR
gene expression in hMADS adipocytes attenuated GW7647 induction of palmitate oxidation. Rosiglitazone had no major impact on glycolysis and
-oxidation. Altogether these results show that PPAR
can selectively up-regulate
-oxidation and decrease glucose utilization in human white adipocytes.
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