The role of estrogen-related receptor α (ERRα) in metabolic adaptations by endurance training in skeletal muscle of streptozotocin-induced diabetic rats

Abstract

The aim of present study was to investigate the effect of endurance training and ERRα inhibition (target for the discovery of new therapies for diseases such as diabetes) on the gene and protein expression of factors involved in lipid metabolism in diabetic rats. We designed the current study to evaluate the combination of ERRα inhibition and exercise training effects on the expression of ERRα, medium-chain acyl-CoA dehydrogenase (MCAD), carnitine palmitoyltransferase-1b (CPT-1b), pyruvate dehydrogenase kinase 4 (PDK4) and Citrate synthase (CS) in diabetic and non-diabetic rats. Sixty-four male Wistar rats were divided into 8 groups (n = 8) as follows: non-diabetic control, diabetic control (a single dose of 45 mg/kg of STZ), non-diabetic/ERRα inhibition group (received 0.48 mg/kg of XCT790), diabetic/ERRα inhibition group, non-diabetic/exercise training, diabetic/exercise training, non-diabetic rats which received XCT790 and performed exercise training, and diabetic rats which received XCT790 and also performed exercise training. The gene and protein expression were measured by real-time PCR (quantified by $$ 2^{{ - \Delta \Delta CT }}$$ method) and Western blotting method, respectively. Our results showed that the expression of ERRα (1.6-fold), MCAD (4.6-fold), CPT-1b (fivefold), CS (twofold), PDK4 (fourfold), and PGC-1α (fourfold) in the medial gastrocnemius muscle of the non-diabetic exercise training group was significantly higher than the non-diabetic control group. In sum, ERRα is a trainable factor, and its changes are parallel with higher expression of the enzymes which involved in lipid metabolism in healthy rats. ERRα inhibition and endurance training may have positive effects on the lipid metabolism in diabetic rats. This indirectly suggests a significant role of ERRα in the adaptation of lipid metabolism evoked by endurance training.