Endurance training and pyruvate dehydrogenase kinase 4 (PDK4) inhibition combination is superior to each one alone in attenuating hyperketonemia/ketoacidosis in diabetic rats
Objective(s): While ketone bodies are not the main heart fuel, exercise may increase their uptake. This study aimed to investigate the effect of 6-week endurance training and Pyruvate dehydrogenase kinase 4 )PDK4( inhibition on ketone bodies metabolism in the heart of diabetic rats with emphasis on...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2025-01-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_25002_07162d0b958cff13974867c66b9b9d0b.pdf |
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| author | Hamed Rezaeinasab Abdolhamid Habibi Ramin Rezaei Aref Basereh Salva Yurista Kayvan Khoramipour |
| author_facet | Hamed Rezaeinasab Abdolhamid Habibi Ramin Rezaei Aref Basereh Salva Yurista Kayvan Khoramipour |
| author_sort | Hamed Rezaeinasab |
| collection | DOAJ |
| description | Objective(s): While ketone bodies are not the main heart fuel, exercise may increase their uptake. This study aimed to investigate the effect of 6-week endurance training and Pyruvate dehydrogenase kinase 4 )PDK4( inhibition on ketone bodies metabolism in the heart of diabetic rats with emphasis on the role of Peroxisome proliferator-activated receptor-gamma coactivator PGC-1alpha (PGC-1α).Materials and Methods: Sixty male Wistar rats were divided into eight groups: healthy control group (CONT), endurance training group (TRA), diabetic group (DM), DM + EX group, Dichloroacetate (DCA) group, DM + DCA group, TRA + DCA group, and DM + TRA + DCA group. Diabetes was induced using streptozotocin (STZ). The animals in training groups ran on the treadmill for six weeks (30–50 min running at 20–30 m/min). After the training period, molecular markers for mitochondrial biogenesis and ketone metabolism were assessed in the heart. Circulating ß-hydroxybutyrate (ßOHB) and Acetylacetonate (AcAc) levels were also measured. Results: Our results showed that 6-week endurance training increased the cardiac expression of PGC-1α, 3-oxoacid CoA-transferase 1 (OXCT1), and Acetyl-CoA Acetyltransferase 1 (ACAT1) and reduced beta-hydroxybutyrate dehydrogenase1 (BDH1) expression (P≤0.05). In addition, exercise and DCA usage significantly decreased PDK4 gene expression, ßOHB, and AcAc blood levels (P≤0.05). Furthermore, the combination of 6-week endurance training and DCA supplementation led to more reduction in PDFK4 gene expression, ßOHB, and AcAc blood levels. Conclusion: Six-week endurance training and DCA supplementation could safely improve ketone body metabolism in the heart, ultimately reducing hyperketonemia/ketoacidosis in diabetic rats. |
| format | Article |
| id | doaj-art-78f6f9d578ce43d697e35f5ccc1aceeb |
| institution | Kabale University |
| issn | 2008-3866 2008-3874 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj-art-78f6f9d578ce43d697e35f5ccc1aceeb2025-08-20T03:56:45ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-01-01281808610.22038/ijbms.2024.79864.1730525002Endurance training and pyruvate dehydrogenase kinase 4 (PDK4) inhibition combination is superior to each one alone in attenuating hyperketonemia/ketoacidosis in diabetic ratsHamed Rezaeinasab0Abdolhamid Habibi1Ramin Rezaei2Aref Basereh3Salva Yurista4Kayvan Khoramipour5Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Shahid Chamran University, Ahvaz, IranDepartment of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Shahid Chamran University, Ahvaz, IranHead of Research and Development Department, Islamic Republic of Iran Basketball FederationDepartment of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Kharazmi University, Tehran, IranHeart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USAi+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), 47012 Valladolid, SpainObjective(s): While ketone bodies are not the main heart fuel, exercise may increase their uptake. This study aimed to investigate the effect of 6-week endurance training and Pyruvate dehydrogenase kinase 4 )PDK4( inhibition on ketone bodies metabolism in the heart of diabetic rats with emphasis on the role of Peroxisome proliferator-activated receptor-gamma coactivator PGC-1alpha (PGC-1α).Materials and Methods: Sixty male Wistar rats were divided into eight groups: healthy control group (CONT), endurance training group (TRA), diabetic group (DM), DM + EX group, Dichloroacetate (DCA) group, DM + DCA group, TRA + DCA group, and DM + TRA + DCA group. Diabetes was induced using streptozotocin (STZ). The animals in training groups ran on the treadmill for six weeks (30–50 min running at 20–30 m/min). After the training period, molecular markers for mitochondrial biogenesis and ketone metabolism were assessed in the heart. Circulating ß-hydroxybutyrate (ßOHB) and Acetylacetonate (AcAc) levels were also measured. Results: Our results showed that 6-week endurance training increased the cardiac expression of PGC-1α, 3-oxoacid CoA-transferase 1 (OXCT1), and Acetyl-CoA Acetyltransferase 1 (ACAT1) and reduced beta-hydroxybutyrate dehydrogenase1 (BDH1) expression (P≤0.05). In addition, exercise and DCA usage significantly decreased PDK4 gene expression, ßOHB, and AcAc blood levels (P≤0.05). Furthermore, the combination of 6-week endurance training and DCA supplementation led to more reduction in PDFK4 gene expression, ßOHB, and AcAc blood levels. Conclusion: Six-week endurance training and DCA supplementation could safely improve ketone body metabolism in the heart, ultimately reducing hyperketonemia/ketoacidosis in diabetic rats.https://ijbms.mums.ac.ir/article_25002_07162d0b958cff13974867c66b9b9d0b.pdfdietary supplementsendurance traininggene expressionketone bodiesketosispyruvate dehydrogenase - kinase 4 |
| spellingShingle | Hamed Rezaeinasab Abdolhamid Habibi Ramin Rezaei Aref Basereh Salva Yurista Kayvan Khoramipour Endurance training and pyruvate dehydrogenase kinase 4 (PDK4) inhibition combination is superior to each one alone in attenuating hyperketonemia/ketoacidosis in diabetic rats Iranian Journal of Basic Medical Sciences dietary supplements endurance training gene expression ketone bodies ketosis pyruvate dehydrogenase - kinase 4 |
| title | Endurance training and pyruvate dehydrogenase kinase 4 (PDK4) inhibition combination is superior to each one alone in attenuating hyperketonemia/ketoacidosis in diabetic rats |
| title_full | Endurance training and pyruvate dehydrogenase kinase 4 (PDK4) inhibition combination is superior to each one alone in attenuating hyperketonemia/ketoacidosis in diabetic rats |
| title_fullStr | Endurance training and pyruvate dehydrogenase kinase 4 (PDK4) inhibition combination is superior to each one alone in attenuating hyperketonemia/ketoacidosis in diabetic rats |
| title_full_unstemmed | Endurance training and pyruvate dehydrogenase kinase 4 (PDK4) inhibition combination is superior to each one alone in attenuating hyperketonemia/ketoacidosis in diabetic rats |
| title_short | Endurance training and pyruvate dehydrogenase kinase 4 (PDK4) inhibition combination is superior to each one alone in attenuating hyperketonemia/ketoacidosis in diabetic rats |
| title_sort | endurance training and pyruvate dehydrogenase kinase 4 pdk4 inhibition combination is superior to each one alone in attenuating hyperketonemia ketoacidosis in diabetic rats |
| topic | dietary supplements endurance training gene expression ketone bodies ketosis pyruvate dehydrogenase - kinase 4 |
| url | https://ijbms.mums.ac.ir/article_25002_07162d0b958cff13974867c66b9b9d0b.pdf |
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