Author/Authors :
Marefati ، Hamid Physiology Research Center, Institute of Basic and Clinical Physiology Sciences - Kerman University of Medical Sciences , Masoumi-Ardakani ، Yaser Physiology Research Center, Institute of Basic and Clinical Physiology Sciences - Kerman University of Medical Sciences , Shakerian ، Saeed Department of Exercise Physiology - Faculty of Physical Education and Sport Sciences - Shahid Chamran University of Ahvaz , Aminizadeh ، Soheil Physiology Research Center, Institute of Basic and Clinical Physiology Sciences - Kerman University of Medical Sciences , Shahouzehi ، Beydolah Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences Student Research Committee - Kerman University of Medical Sciences , Habibi ، Abdolhamid Department of Exercise Physiology - Faculty of Physical Education and Sport Sciences - Shahid Chamran University of Ahvaz
Abstract :
Metabolic flexibility is the capacity of a system to adjust fuel (primarily glucose and fatty acids) oxidation based on nutrient availability. Pyruvate Dehydrogenase Kinase 4 (PDK4) is one of the main enzymes that play a critical role in metabolic flexibility. In current study, we examined PDK4 inhibition along with exercise training (ET) on the gene expression of Estrogen related-receptor alpha (ERRα), medium-chain acyl-CoA dehydrogenase (MCAD), carnitine palmitoyl transferase-1b (CPT-1b), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), PDK4 and citrate synthase (CS) in skeletal muscle. Sixty-four male Wistar rats (8 week-old) were randomly divided into 8 groups (n=8); 1- untreated control, 2- STZ-induced diabetic, 3- PDK4 inhibition, 4- endurance training (ET), 5- diabetic + PDK4 inhibition, 6- diabetic + ET, 7- PDK4 inhibition + ET, and 8- diabetic +ET + PDK4 inhibition. ERRα, MCAD, CPT-1b, PGC-1α, PDK4 and CS genes expressions were measured by Real-Time PCR and quantified by 2-ΔΔCt method. ERRα, MCAD, CPT-1b, PGC-1α, PDK4, and CS expressions were significantly higher in non-diabetic+ Endurance Training group compared to the control group. The expressions of CPT-1b, MCAD and CS genes were significantly lower in the non-diabetic+ endurance training/PDK4 inhibition compared to the non-diabetic+ endurance training group, and the expressions of ERRα, CPT-1b and MCAD were significantly lower in the diabetic + PDK4 inhibition group compared to the diabetic group. In sum, PDK4 inhibition has negative effects on lipid metabolism in healthy rats, but in animals with diabetes, PDK4 inhibition can be used for improving lipid metabolism (over-expression of CS and PGC-1α).
