Thiazolidinediones Upregulate Fatty Acid Uptake and Oxidation in Adipose Tissue of Diabetic Patients

Thiazolidinediones Upregulate Fatty Acid Uptake and Oxidation in Adipose Tissue of Diabetic Patients Guenther Boden 1 2 , Carol Homko 2 , Maria Mozzoli 1 2 , Louise C. Showe 3 , Calen Nichols 3 and Peter Cheung 1 2 1 Division of Endocrinology, Diabetes, and Metabolism, Temple University School of Medicine, Philadelphia, Pennsylvania 2 General Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 3 Wistar Institute, Philadelphia, Pennsylvania Address correspondence and reprint requests to Guenther Boden, MD, Temple University Hospital, 3401 N. Broad St., Philadelphia, PA 19140. E-mail: bodengh{at}tuhs.temple.edu Abstract Thiazolidinediones (TZDs) are a new class of insulin-sensitizing drugs. To explore how and in which tissues they improve insulin action, we obtained fat and muscle biopsies from eight patients with type 2 diabetes before and 2 months after treatment with rosiglitazone ( n = 5) or troglitazone ( n = 3). TZD treatment was associated with a coordinated upregulation in the expression of genes and synthesis of proteins involved in fatty acid uptake, binding, β-oxidation and electron transport, and oxidative phosphorylation in subcutaneous fat but not in skeletal muscle. These changes were accompanied by a 13% increase in total body fat oxidation, a 20% decrease in plasma free fatty acid levels, and a 46% increase in insulin-stimulated glucose uptake. We conclude that TZDs induced a coordinated stimulation of fatty acid uptake, oxidation, and oxidative phosphorylation in fat of diabetic patients and thus may have corrected, at least partially, a recently recognized defect in patients with type 2 diabetes consisting of reduced expression of genes related to oxidative metabolism and mitochondrial function. ACADM, acyl-CoA dehydrogenase FFA, free fatty acid FOX, fatty acid oxidation HCS, cytochrome C PPARγ, peroxisome proliferator-activated receptor γ TZD, thiazolidinedione Footnotes Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org . Accepted December 9, 2004. Received July 14, 2004. DIABETES