Hamid Marefati - Associate Professor, Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
Yaser Masoumi-Ardakani - Ph.D. Candidate, Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
Saeed Shakerian - Associate Professor, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Abdolhamid Habibi - Associate Professor, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Soheil Aminizadeh - Assistant Professor, Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
Beydolah Shahouzehi - Assistant Professor, Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences & Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran

Background:Metabolic flexibility is the capacity of a system to adjust fuel (primarily glucose and fatty acids) oxidation based on nutrient availability. Pyruvate Dehydrogenase Kinase ۴ (PDK۴) is one of the main enzymes that play a critical role in metabolic flexibility. In current study, we examined PDK۴ 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-۱b (CPT-۱b), peroxisome proliferator-activated receptor gamma coactivator ۱-alpha (PGC-۱α), PDK۴ and citrate synthase (CS) in skeletal muscle.Method:Sixty-four male Wistar rats (۸ week-old) were randomly divided into ۸ groups (n=۸); ۱- untreated control, ۲- STZ-induced diabetic, ۳- PDK۴ inhibition, ۴- endurance training (ET), ۵- diabetic + PDK۴ inhibition, ۶- diabetic + ET, ۷- PDK۴ inhibition + ET, and ۸- diabetic +ET + PDK۴ inhibition. ERRα, MCAD, CPT-۱b, PGC-۱α, PDK۴ and CS genes expressions were measured by Real-Time PCR and quantified by ۲-ΔΔCt method.Results:ERRα, MCAD, CPT-۱b, PGC-۱α, PDK۴, and CS expressions were significantly higher in non-diabetic+ Endurance Training group compared to the control group. The expressions of CPT-۱b, MCAD and CS genes were significantly lower in the non-diabetic+ endurance training/PDK۴ inhibition compared to the non-diabetic+ endurance training group, and the expressions of ERRα, CPT-۱b and MCAD were significantly lower in the diabetic + PDK۴ inhibition group compared to the diabetic group.Conclusion:In sum, PDK۴ inhibition has negative effects on lipid metabolism in healthy rats, but in animals with diabetes, PDK۴ inhibition can be used for improving lipid metabolism (over-expression of CS and PGC-۱α).

Pyruvate Dehydrogenase Kinase ۴ Endurance Training Metabolic Flexibility Estrogen, Related Receptor