Type 2 diabetes has been related to a decrease of mitochondrial DNA (mtDNA) content. In this study, we show increased expression of the peroxisome proliferator-activated receptor-␣ (PPAR ␣ ) and its target genes involved in fatty acid metabolism in skeletal muscle of Zucker Diabetic Fatty (ZDF) ( fa/fa ) rats. In contrast, the mRNA levels of genes involved in glucose transport and utilization (GLUT4 and phosphofructokinase) were decreased, whereas the expression of pyruvatedehydrogenase kinase

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... (PDK-4), which suppresses glucose oxidation, was increased. The shift from glucose to fatty acids as the source of energy in skeletal muscle of ZDF rats was accompanied by a reduction of subunit 1 of complex I (NADH dehydrogenase subunit 1, ND1) and subunit II of complex IV (cytochrome c oxidase II, COII), two genes of the electronic transport chain encoded by mtDNA. The transcript levels of PPAR ␥ Coactivator 1 (PGC-1) showed a significant reduction. Treatment with troglitazone (30 mg/ kg/day) for 15 days reduced insulin values and reversed the increase in PDK-4 mRNA levels, suggesting improved insulin sensitivity. In addition, troglitazone treatment restored ND1 and PGC-1 expression in skeletal muscle. These results suggest that troglitazone may avoid mitochondrial metabolic derangement during the development of diabetes mellitus 2 in skeletal muscle. -Jové, M., J. Salla, A. Planavila, À. Cabrero, L. Michalik, W. Wahli, J. C. Laguna, and M. Vázquez-Carrera. Impaired expression of NADH dehydrogenase subunit 1 and PPAR ␥ coactivator-1 in skeletal muscle of ZDF rats: restoration by troglitazone. J. Lipid Res . 2004. 45: 113-123.