Hyperglycemic diet and training alter insulin sensitivity, intramyocellular lipid content but not UCP3 protein expression in rat skeletal muscles

Abstract

Abstract. Intramyocellular lipids (IMCL) and mitochondrial uncoupling protein-3 (UCP3) have been implicated in the development of muscular insulin resistance. This study aimed to investigate the role of IMCL and UCP3 in the development of glucose intolerance and muscular insulin resistance during 12 weeks of an obesity-inducing 'cafeteria-style' diet alone (CAF), or in conjunction with exercise training from weeks 8-12 (CAF TR ), in rats. At the end of the intervention period, gain in body weight was 20% higher in CAF (305±10 g) than controls (CON) (255±14 g; p<0.001) and CAF TR (253±7 g; p<0.001). Furthermore, compared with CON, the Matsuda insulin sensitivity index (ISI), assessed during a 2-h intravenous glucose tolerance test, was markedly lower in CAF (6.7±0.4) than in either CON (15.6±1.4; p<0.001) or CAF TR (11.2±1.1; p<0.001). Moreover, in CAF glucose transport at a submaximal insulin concentration (200 μU/ml) was reduced by ~60% (p<0.05) in both red and white gastrocnemius muscles, but not in m. soleus. However, glucose transport in CAF TR was similar to CON in red gastrocnemius. In CAF fiber-specific IMCL content determined in m. soleus and extensor digitorum longus (EDL), was higher than in CON (p<0.01) and CAF TR (p<0.001). Muscle UCP3 protein content was not changed by any of the interventions. Interestingly, within CAF and CAF TR , ISI closely negatively correlated with IMCL content in both type I (soleus, r=-0.93; EDL, r=-0.90; p<0.05) and IIa (EDL, r=-0.52, p<0.05) muscle fibers. These findings indicate that changes in IMCL content but not UCP3 content are implicated in short-term effects of cafeteria-style diet and exercise training on muscular insulin sensitivity in rats.