Peroxisome proliferator-activated receptor-alpha control of lipid and glucose metabolism in human white adipocytes.
This work aimed at characterizing the role of peroxisome proliferator-activated receptors (PPAR)alpha in human white adipocyte metabolism and at comparing PPAR alpha and PPAR gamma actions in these cells. Primary cultures of human fat cells were treated with the PPAR alpha agonist GW7647 or the PPAR gamma agonist rosiglitazone. Changes in gene expression were determined using DNA microarrays 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 beta-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 alpha agonist. GW7647-induced alterations were abolished by a treatment with a PPAR alpha antagonist. Small interfering RNA-mediated extinction of PPAR alpha gene expression in hMADS adipocytes attenuated GW7647 induction of palmitate oxidation. Rosiglitazone had no major impact on glycolysis and beta-oxidation. Altogether these results show that PPAR alpha can selectively up-regulate beta-oxidation and decrease glucose utilization in human white adipocytes.
Ribet
Carole
C
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 858, 1 Avenue Jean Pouilhès, BP 84225, 31432 Toulouse Cedex 4, France.
Montastier
Emilie
E
Valle
Carine
C
Bezaire
Véronic
V
Mazzucotelli
Anne
A
Mairal
Aline
A
Viguerie
Nathalie
N
Langin
Dominique
D
D052438:Adipocytes, White / Q000187:drug effects / Q000378:metabolism*; D002087:Butyrates / Q000494:pharmacology; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D047495:PPAR gamma / Q000819:agonists / Q000502:physiology; D010671:Phenylurea Compounds / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
D002087:Butyrates; D005227:Fatty Acids; C453899:GW 7647; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D010671:Phenylurea Compounds; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005947:Glucose