Abstract

Objective: In the present experiment, insulin sensitivity and glucose metabolism was compared in rats that were fed a HFD diet for 12 weeks compared to those fed an LFD diet. Methods: Sixteen male Sprague-Dawley rats (n = 8 per group) were randomised to an LFD (10% kcal fat) and HFD (60% kcal fat) for 12 weeks. Parameters assessed were an OGTT, the HOMA-IR index, in vitro uptake of [2-DG] by isolated soleus muscle, Western blotting for GLUT4 and phospho-Akt, plasma levels of inflammation mediators and muscle histology with hematoxylin-eosin and Oil Red O staining. Results: The HFD group had significantly greater terminal body weight, epididymal adiposity, fasting glucose and HOMA-IR index than the control group. At a muscle level, GLUT4 protein level was decreased by 39%, insulin-stimulated 2-DG uptake by 44% and the p-Akt(Ser473)/total-Akt ratio by 48%. Increased Oil Red O-positive lipid stores and decreased fibre CSA were observed in the soleus muscles of the HFD group. The correlation between the HOMA-IR index and GLUT4 protein levels and 2-DG uptake was inverse. Conclusion: Rats do not have insulin sensitivity which is reliably and statistically reduced after a 12 week high fat feeding period, both in the system and at the muscle level.

Keywords: Insulin resistance, Skeletal muscle, High-fat diet, Glucose uptake