Pioglitazone Induces Mitochondrial Biogenesis in Human Subcutaneous Adipose Tissue In Vivo

  1. Iwona Bogacka,
  2. Hui Xie,
  3. George A. Bray and
  4. Steven R. Smith
  1. From the Molecular Endocrinology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana
  1. Address correspondence and reprint requests to Iwona Bogacka, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA. E-mail: bogackiu{at}pbrc.edu

Abstract

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. Mitochodrial 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)-γ coactivator-1α 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-α, 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.

Footnotes

  • I.B. has received grant/research support from Takeda Pharmaceuticals. H.X. has received grant/research support from Takeda Pharmaceuticals. G.A.B. has served on an advisory board of, has received honoraria from, and has received grant/research support from Takeda Pharmaceuticals. S.R.S. has received honoraria/consulting fees and research support from Takeda Pharmaceuticals.

    • Accepted February 17, 2005.
    • Received June 23, 2004.
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