Distinct Gene Expression Profile Distinguishes Increased Metabolic Activity in Spontaneously Hyperactive Rats While Sedentary from That Induced by Exercise

Abstract

The Spontaneously-Running Tokushima Shikoku (SPORTS) strain is an original line derived from Wistar rats, which spontaneously runs >6 km/day on wheels, and has better glucose tolerance and less fat than Wistar rats. However, the molecular mechanism that contributes to the increased metabolic activity in SPORTS rats is unknown. The present study aimed to characterize the gene expression profiles of skeletal muscles in SPORTS rats housed under sedentary (SED) conditions. We found that the expression levels of genes encoding mitochondrial respiratory chain enzymes such as ATP synthase 6 (mt-Atp6) and cytochrome c oxidase subunit 6c (Cox6c), were higher in the soleus (SOL) muscles of SED SPORTS than in SED Wistar rats. The ratio of type IIa myofibers was higher and glucose tolerance was better in SED SPORTS than in Wistar rats that were sedentary and trained daily on treadmills, respectively. We then investigated candidate genes that might contribute to the better glucose tolerance of SED SPORTS rats using DNA microarray analysis. Among 116 upregulated genes in the SOL muscles of SED SPORTS rats, only 19 were also increased in trained Wistar rats. We focused on v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (Erbb3), which was associated with glucose transport in myocytes, and found higher expression levels in the SOL muscles of SED SPORTS than in SED Wistar rats. The SOL muscles of SED SPORTS rats also contained more activity of β-hydroxyacylCoA dehydrogenase, a key enzyme of β-oxidation, indicating enhanced lipid oxidation. These findings suggest that increased metabolic activity in skeletal muscle (especially the SOL muscle) of SPORTS rats is congenital and that gene expression profiles of SPORTS rats and Trained Wistar rats are different.