Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo.
Thiazolidenediones such as pioglitazone improve insulin sensitivity in diabetic patients by several mechanisms, including increased uptake and metabolism of free fatty acids in adipose tissue. The purpose of the present study was to determine the effect of pioglitazone on mitochondrial biogenesis and expression of genes involved in fatty acid oxidation in subcutaneous fat. Patients with type 2 diabetes were randomly divided into two groups and treated with placebo or pioglitazone (45 mg/day) for 12 weeks. Mitochondrial DNA copy number and expression of genes involved in mitochondrial biogenesis were quantified by real-time PCR. Pioglitazone treatment significantly increased mitochondrial copy number and expression of factors involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1alpha and mitochondrial transcription factor A. Treatment with pioglitazone stimulated the expression of genes in the fatty acid oxidation pathway, including carnitine palmitoyltransferase-1, malonyl-CoA decarboxylase, and medium-chain acyl-CoA dehydrogenase. The expression of PPAR-alpha, a transcriptional regulator of genes encoding mitochondrial enzymes involved in fatty acid oxidation, was higher after pioglitazone treatment. Finally, the increased mitochondrial copy number and the higher expression of genes involved in fatty acid oxidation in human adipocytes may contribute to the hypolipidemic effects of pioglitazone.
Bogacka
Iwona
I
Molecular Endocrinology Laboratory, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, USA. bogackiu@pbrc.edu
Xie
Hui
H
Bray
George A
GA
Smith
Steven R
SR
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology*; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D047495:PPAR gamma / Q000235:genetics; D000077205:Pioglitazone; D016133:Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*
D004272:DNA, Mitochondrial; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone