The Effects of Pyruvate Dehydrogenase Kinase ۴ (PDK۴) Inhibition on Metabolic Flexibility during Endurance Training in Skeletal Muscles of Streptozotocin-induced Diabetic Rats

سال انتشار: 1399
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 122

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شناسه ملی سند علمی:

JR_JKMU-27-4_003

تاریخ نمایه سازی: 19 دی 1401

چکیده مقاله:

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).

کلیدواژه ها:

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

نویسندگان

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

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