The temporal changes in skeletal muscle mitochondrial content and lipid metabolism that precede type 2 diabetes are largely unknown. Here we examined skeletal muscle mitochondrial fatty acid oxidation (MitoFAOX) and markers of mitochondrial gene expression and protein content in sedentary 20 and 40 week old hyperphagic, obese Otsuka Long-Evans Tokushima Fatty (OLETF-SED) rats. Changes in OLETF-SED rats were compared to two groups of rats who maintained insulin sensitivity: age-matched OLETF rats given access to voluntary running wheels (OLETF-EX) and sedentary, nonobese Long-Evans Tokushima Otsuka (LETO-SED) rats. As expected, glucose tolerance tests revealed insulin resistance at 20 weeks that progressed to type 2 diabetes at 40 weeks in the OLETF-SED, while both the OLETF-EX and LETO-SED maintained whole body insulin sensitivity. At 40 weeks, complete MitoFAOX (to CO2), β-hydroxyacyl-CoA dehydrogenase activity, and citrate synthase activity did not differ between OLETF-SED and LETO-SED, but were significantly (p<0.05) higher in OLETF-EX compared with OLETF-SED rats. Genes controlling skeletal muscle mitochondrial fatty acid oxidation (PGC1α, PPARδ, mtTFA, cytochrome c) were not different between OLETF-SED and LETO-SED at any age. Compared to the OLETF-SED, the OLETF-EX rats had significantly (p<0.05) higher skeletal muscle PGC-1α, cytochrome c, and mtTFA mRNA levels at 20 and 40 weeks and PPARδ at 40 weeks; however, protein content for each of these markers did not differ between groups at 40 weeks. Conclusions: Limited changes in skeletal muscle mitochondria were observed during the transition from insulin resistance to type 2 diabetes in the hyperphagic OLETF rat. However, diabetes prevention through increased physical activity appears to be mediated in part through maintenance of skeletal muscle mitochondrial function.
- skeletal muscle mitochondria
- type 2 diabetes
- insulin resistance
- Copyright © 2009, American Journal of Physiology - Endocrinology and Metabolism