1- Department of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran , md.khajehlandi@uma.ac.ir
2- Department of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran
2- Department of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran
Abstract: (334 Views)
Background: Mitochondrial function is an integral part of glucose-stimulated insulin secretion in pancreatic β-cells and is a hallmark feature of cardiovascular disease. It may contribute to the pathophysiology of diabetic cardiomyopathy and atherosclerosis. This study aimed to investigate the effect of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), combined with quercetin supplementation (eight weeks), on mitochondrial gene expression in the diabetic heart.
Methods: In this study, 35 adult male rats were equally divided into seven groups (n=5): healthy sedentary, diabetic sedentary, diabetic quercetin sedentary, diabetic HIIT (DHIIT), diabetic MICT (DMICT), DHIIT with quercetin, and DMICT with quercetin. The rats were fed a high-fat diet for eight weeks and subsequently treated with a single low dose of streptozotocin to create a model of type 2 diabetes mellitus (T2DM). Eight weeks (five times a week) of HIIT and MICT, with and without quercetin, were conducted for the training groups, and quercetin was injected over eight weeks at a dose of 15 mg/kg.
Results: Eight weeks of quercetin supplementation, HIIT, and MICT, with and without quercetin, significantly decreased blood glucose levels (P=0.001). Eight weeks of HIIT and MICT training increased nuclear respiratory factor-2 (NRF2) (P=0.001) and adipose triglyceride lipase (ATGL) (P=0.001) expression and decreased perilipin 2 (PLIN2) gene expression (P=0.001).
Conclusion: The training groups alone improved the gene expression of NRF2, ATGL, and PLIN2. Both training protocols, combined with quercetin, controlled blood glucose levels and improved antioxidant capacity. Thus, the reduction in blood glucose through quercetin supplementation appears to be a promising approach for managing T2DM.
Methods: In this study, 35 adult male rats were equally divided into seven groups (n=5): healthy sedentary, diabetic sedentary, diabetic quercetin sedentary, diabetic HIIT (DHIIT), diabetic MICT (DMICT), DHIIT with quercetin, and DMICT with quercetin. The rats were fed a high-fat diet for eight weeks and subsequently treated with a single low dose of streptozotocin to create a model of type 2 diabetes mellitus (T2DM). Eight weeks (five times a week) of HIIT and MICT, with and without quercetin, were conducted for the training groups, and quercetin was injected over eight weeks at a dose of 15 mg/kg.
Results: Eight weeks of quercetin supplementation, HIIT, and MICT, with and without quercetin, significantly decreased blood glucose levels (P=0.001). Eight weeks of HIIT and MICT training increased nuclear respiratory factor-2 (NRF2) (P=0.001) and adipose triglyceride lipase (ATGL) (P=0.001) expression and decreased perilipin 2 (PLIN2) gene expression (P=0.001).
Conclusion: The training groups alone improved the gene expression of NRF2, ATGL, and PLIN2. Both training protocols, combined with quercetin, controlled blood glucose levels and improved antioxidant capacity. Thus, the reduction in blood glucose through quercetin supplementation appears to be a promising approach for managing T2DM.
Keywords: Exercise, Gene Expression, Genome, Mitochondrial, Quercetin, ATGL-1 protein, PLIN2 protein, human
References
1. Klein S, Gastaldelli A, Yki-Järvinen H, Scherer PE. Why does obesity cause diabetes? Cell Metab. 2022;34(1):11-20. [View at Publisher] [DOI] [PMID] [Google Scholar]
2. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995;122(7):481-6. [View at Publisher] [DOI] [PMID] [Google Scholar]
3. Moreno-Indias I, Tinahones FJ. Impaired adipose tissue expandability and lipogenic capacities as ones of the main causes of metabolic disorders. J Diabetes Res. 2015;2015(1):970375. [View at Publisher] [DOI] [PMID] [Google Scholar]
4. Braunwald E. Diabetes, heart failure, and renal dysfunction: the vicious circles. Prog Cardiovasc Dis. 2019;62(4):298-302. [View at Publisher] [DOI] [PMID] [Google Scholar]
5. Boudina S, Abel ED. Diabetic cardiomyopathy, causes and effects.Rev Endocr Metab Disord. 2010;11(1):31-9. [View at Publisher] [DOI] [PMID] [Google Scholar]
6. Li Y, Feng YF, Liu XT, Li YC, Zhu HM, Sun MR, et al. Songorine promotes cardiac mitochondrial biogenesis via Nrf2 induction during sepsis. Redox Biol. 2021;38:101771. [View at Publisher] [DOI] [PMID] [Google Scholar]
7. Piantadosi CA, Carraway MS, Babiker A, Suliman HB. Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1. Circ Res. 2008;103(11):1232-40. [View at Publisher] [DOI] [PMID] [Google Scholar]
8. Sato S, Suzuki J, Hirose M, Yamada M, Zenimaru Y, Nakaya T, et al. Cardiac overexpression of perilipin 2 induces atrial steatosis, connexin 43 remodeling, and atrial fibrillation in aged mice. Am J Physiol Endocrinol Metab. 2019;317(6):E1193-204. [View at Publisher] [DOI] [PMID] [Google Scholar]
9. Greenberg AS, Coleman RA, Kraemer FB, McManaman JL, Obin MS, Puri V, et al. The role of lipid droplets in metabolic disease in rodents and humans. J Clin Invest. 2011;121(6):2102-10. [View at Publisher] [DOI] [PMID] [Google Scholar]
10. Da Dalt L, Cabodevilla AG, Goldberg IJ, Norata GD. Cardiac lipid metabolism, mitochondrial function, and heart failure. Cardiovasc Res. 2023;119(10):1905-14. [View at Publisher] [DOI] [PMID] [Google Scholar]
11. Straub BK, Gyoengyoesi B, Koenig M, Hashani M, Pawella LM, Herpel E, et al. Adipophilin/perilipin‐2 as a lipid droplet‐specific marker for metabolically active cells and diseases associated with metabolic dysregulation. Histopathology. 2013;62(4):617-31. [View at Publisher] [DOI] [PMID] [Google Scholar]
12. Huang W, Gao F, Zhang Y, Chen T, Xu C. Lipid droplet-associated proteins in cardiomyopathy. Ann Nutr Metab. 2022;78(1):1-13. [View at Publisher] [DOI] [PMID] [Google Scholar]
13. Kaur S, Auger C, Barayan D, Shah P, Matveev A, Knuth CM, et al. Adipose‐specific ATGL ablation reduces burn injury‐induced metabolic derangements in mice. Clin Transl Med. 2021;11(6):e417. [View at Publisher] [DOI] [PMID] [Google Scholar]
14. Prats C, Donsmark M, Qvortrup K, Londos C, Sztalryd C, Holm C, et al. Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine. J Lipid Res. 2006;47(11):2392-9. [View at Publisher] [DOI] [PMID] [Google Scholar]
15. Cereijo L, Gullón P, Del Cura I, Valadés D, Bilal U, Badland H, et al. Exercise facilities and the prevalence of obesity and type 2 diabetes in the city of Madrid. Diabetologia. 2022;65(1):150-8. [View at Publisher] [DOI] [PMID] [Google Scholar]
16. Bennetsen SL, Feineis CS, Legaard GE, Lyngbæk MP, Karstoft K, Ried-Larsen M. The impact of physical activity on glycemic variability assessed by continuous glucose monitoring in patients with type 2 diabetes mellitus: a systematic review. Front Endocrinol (Lausanne). 2020;11:486. [View at Publisher] [DOI] [PMID] [Google Scholar]
17. Esefeld K, Kress S, Behrens M, Zimmer P, Stumvoll M, Thurm U, et al. Diabetes, sports and exercise. Exp Clin Endocrinol Diabetes. 2021;129(S01):S52-9. [View at Publisher] [DOI] [PMID] [Google Scholar]
18. Yu H, Zhao X, Wu X, Yang J, Wang J, Hou L. High-intensity interval training versus moderate-intensity continuous training on patient quality of life in cardiovascular disease: A systematic review and meta-analysis. Sci Rep. 2023;13(1):13915. [View at Publisher] [DOI] [PMID] [Google Scholar]
19. Chiş I, Baltaru D, Dumitrovici A, Coseriu A, Radu B, Moldovan R, et al. Protective effects of quercetin from oxidative/nitrosative stress under intermittent hypobaric hypoxia exposure in the rat's heart. Physiol Int. 2018;105(3):233-46. [View at Publisher] [DOI] [PMID] [Google Scholar]
20. Kamboj S, Mukhija M, Monga J, Singla R, Chaudhary J. Mechanistic investigation of Quercetin in the management of complications of Diabetes mellitus by Network Pharmacology. J Mol Chem. 2024;4(1):684. [View at Publisher] [Google Scholar]
21. Egan B, Sharples AP. Molecular responses to acute exercise and their relevance for adaptations in skeletal muscle to exercise training. Physiol Rev. 2023;103(3):2057-170. [View at Publisher] [DOI] [PMID] [Google Scholar]
22. Engel LE, de Souza FLA, Giometti IC, Okoshi K, Mariano TB, Ferreira NZ, et al. The high-intensity interval training mitigates the cardiac remodeling in spontaneously hypertensive rats. Life Sci. 2022;308:120959. [View at Publisher] [DOI] [PMID] [Google Scholar]
23. Ramos SV, Turnbull PC, MacPherson RE. Adipose tissue depot specific differences of PLIN protein content in endurance trained rats. Adipocyte. 2016;5(2):212-23. [View at Publisher] [DOI] [PMID] [Google Scholar]
24. Khajehlandi M, Bolboli L. The effect of eight weeks of high-intensity interval and moderate-intensity continuous training with quercetin supplementation on the expression of PGC1-α and NRF-1 genes in the heart tissue of obese diabetic male rats. Feyz Med Sci J. 2024;28(1):58-67. [View at Publisher] [DOI] [Google Scholar]
25. Eitah HE, Maklad YA, Abdelkader NF, El Din AAG, Badawi MA, Kenawy SA. Modulating impacts of quercetin/sitagliptin combination on streptozotocin-induced diabetes mellitus in rats. Toxicol Appl Pharmacol. 2019;365:30-40. [View at Publisher] [DOI] [PMID] [Google Scholar]
26. Pengam M, Goanvec C, Moisan C, Simon B, Albacète G, Féray A, et al. Moderate intensity continuous versus high intensity interval training: Metabolic responses of slow and fast skeletal muscles in rat. Plos one. 2023;18(10):e0292225. [View at Publisher] [DOI] [PMID] [Google Scholar]
27. Dupas J, Feray A, Guernec A, Pengam M, Inizan M, Guerrero F, et al. Effect of personalized moderate exercise training on Wistar rats fed with a fructose enriched water. Nutr Metab (Lond). 2018;15(1):69. [View at Publisher] [DOI] [PMID] [Google Scholar]
28. Bahadoran Z, Golzarand M, Mirmiran P, Saadati N, Azizi F. The association of dietary phytochemical index and cardiometabolic risk factors in adults: Tehran Lipid and Glucose Study. J Hum Nutr Diet. 2013;26(S1):145-53. [View at Publisher] [DOI] [PMID] [Google Scholar]
29. Yang H, Yang T, Heng C, Zhou Y, Jiang Z, Qian X, et al. Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice. Phytother Res. 2019;33(12):3140-52. [View at Publisher] [DOI] [PMID] [Google Scholar]
30. Boots AW, Drent M, de Boer VC, Bast A, Haenen GR. Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis. Clin Nutr. 2011;30(4):506-12. [View at Publisher] [DOI] [PMID] [Google Scholar]
31. Azeem M, Hanif M, Mahmood K, Ameer N, Chughtai FRS, Abid U. An insight into anticancer, antioxidant, antimicrobial, antidiabetic and anti-inflammatory effects of quercetin: A review. Polym Bull (Berl). 2023;80(1):241-62. [View at Publisher] [DOI] [PMID] [Google Scholar]
32. Cherry AD, Piantadosi CA. Regulation of mitochondrial biogenesis and its intersection with inflammatory responses. Antioxid Redox Signal. 2015;22(12):965-76. [View at Publisher] [DOI] [PMID] [Google Scholar]
33. Michaličková D, Hrnčíř T, Canová NK, Slanař O. Targeting Keap1/Nrf2/ARE signaling pathway in multiple sclerosis. Eur J Pharmacol. 2020;873:172973. [View at Publisher] [DOI] [PMID] [Google Scholar]
34. Done AJ, Gage MJ, Nieto NC, Traustadóttir T. Exercise-induced Nrf2-signaling is impaired in aging. Free Radic Biol Med. 2016;96:130-8. [View at Publisher] [DOI] [PMID] [Google Scholar]
35. Dinkova-Kostova AT, Abramov AY. The emerging role of Nrf2 in mitochondrial function. Free Radic Biol Med. 2015;88(Pt B):179-88. [View at Publisher] [DOI] [PMID] [Google Scholar]
36. Pino-de la Fuente F, Bórquez JC, Díaz-Castro F, Espinosa A, Chiong M, Troncoso R. Exercise regulation of hepatic lipid droplet metabolism. Life Sci. 2022;298:120522. [View at Publisher] [DOI] [PMID] [Google Scholar]
37. Shaw CS, Shepherd SO, Wagenmakers AJ, Hansen D, Dendale P, Van Loon LJ. Prolonged exercise training increases intramuscular lipid content and perilipin 2 expression in type I muscle fibers of patients with type 2 diabetes. Am J Physiol Endocrinol Metab. 2012;303(9):E1158-65. [View at Publisher] [DOI] [PMID] [Google Scholar]
38. Fritsch LJ, McCaulley SJ, Johnson CR, Lawson NJ, Gorres-Martens BK. Exercise prevents whole body type 2 diabetes risk factors better than estradiol replacement in rats. J Appl Physiol. 2021;131(5):1520-31. [View at Publisher] [DOI] [PMID] [Google Scholar]
39. Sugimoto T, Uchitomi R, Onishi T, Kamei Y. A combination of exercise and calorie restriction improves the development of obesity-related type 2 diabetes mellitus in KKAy mice. Biosci Biotechnol Biochem. 2023;87(1):108-13. [View at Publisher] [DOI] [PMID] [Google Scholar]
40. Li R, Li G, Hai Y, Li T, Bian Y, Ma T. The effect of aerobic exercise on the lipophagy of adipose tissue in obese male mice. Chem Phys Lipids. 2022;247:105225. [View at Publisher] [DOI] [PMID] [Google Scholar]
41. Yang Y, Li X, Liu Z, Ruan X, Wang H, Zhang Q, et al. Moderate Treadmill Exercise Alleviates NAFLD by Regulating the Biogenesis and Autophagy of Lipid Droplet. Nutrients. 2022;14(22):4910. [View at Publisher] [DOI] [PMID] [Google Scholar]
42. Pino-de la Fuente F, Quezada L, Sepúlveda C, Monsalves-Alvarez M, Rodríguez JM, Sacristan C, et al. Exercise regulates lipid droplet dynamics in normal and fatty liver. Biochim Biophys Acta Mol Cell Biol Lipids. 2019;1864(12):158519. [View at Publisher] [DOI] [PMID] [Google Scholar]
43. Louche K, Badin P-M, Montastier E, Laurens C, Bourlier V, de Glisezinski I, et al. Endurance exercise training up-regulates lipolytic proteins and reduces triglyceride content in skeletal muscle of obese subjects. J Clin Endocrinol Metab. 2013;98(12):4863-71. [View at Publisher] [DOI] [PMID] [Google Scholar]
44. Kim C-H, Kim M-S, Youn J-Y, Park H-S, Song H-S, Song KH, et al. Lipolysis in skeletal muscle is decreased in high-fat-fed rats. Metabolism. 2003;52(12):1586-92. [View at Publisher] [DOI] [PMID] [Google Scholar]
45. Wu B, Xu C, Tian Y, Zeng Y, Yan F, Chen A, et al. Aerobic exercise promotes the expression of ATGL and attenuates inflammation to improve hepatic steatosis via lncRNA SRA. Sci Rep. 2022;12(1):5370. [View at Publisher] [DOI] [PMID] [Google Scholar]
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