Investigating the effects of rosiglitazone and epigallocatechin-3-gallate on pgc-la protein expression in palmitate-induced insulin resistant c2c12 skeletal muscle cells

ABSTRACT

Alterations in lipids metabolism are one of the important mechanisms for the treatment of insulin resistance and, hence for type 2 diabetes. On the other hand, PGC-1alpha, as a key regulator of mitochondrial biogenesis and function, by increasing beta-oxidation of lipids plays an important role in improving insulin sensitivity. In the present study, the effects of Epigallocatechin-3-Gallate [EGCG], an anti-obesity and enhancer of lipid catabolism agent, on PGC-1alpha protein expression was examined and compared with the anti-diabetic drug Rosiglitazone [RGZ]. After differentiation of C2C12 myoblasts to myotubes, insulin resistance was induced by palmitate treatment. Afterward, PGC-1alpha protein expression was examined using the western blot method before and after treatment with insulin and after EGCG and RGZ treatment. Palmitate treatment significantly decreased PGC-1 alpha protein expression in the C2C12 cells [P=0.001]. Treatment of these cells with EGCG had no significant effect on the PGC-1 alpha protein expression [P=0.67], whereas treatment with RGZ significantly increased expression of this gene at protein level [P=0.003]. In addition, this significant increase in PGC-1 alpha protein expression was maintained by simultaneous treatment with EGCG and RGZ [P=0.001]. Our results showed that the effect of EGCG on PGC-1 a protein expression was not significant, whereas RGZ significantly improved the palmitate-induced reduction of PGC-1 alpha protein expression. Overall, it seems that anti-diabetic effect of EGCG is not exerted through its effect on the expression of PGC-1alpha gene, in contrast to that of RGZ