The effect of high-intensity interval training and high-protein diet on the levels of UCP-2 and MCP-1 and insulin sensitivity in visceral fat and skeletal muscle of obese male rats

Document Type : Research Paper I Open Access I Released under (CC BY-NC 4.0) license

Authors

1 Department of Sport Sciences, Faculty of Sport Sciences, University of Birjand, Birjand, Iran

2 Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Aims: Exercise training and diet can prevent obesity, inflammation, and insulin resistance. Present study aimed to investigate the effect of 10 weeks of high-intensity interval training (HIIT) and high-protein diet (HPD) on the levels of UCP-2 and MCP-1 in visceral fat tissue and gastrocnemius muscle, plasma levels of glucose and insulin, and insulin sensitivity. Methods: Forty obese male Wistar rats (weight 386.46±31.79 g) into five group included: HIIT, HPD, HIIT+ HPD, obese control-1 (OC-1: having high-fat diet during intervention), and obese control-2 (OC-2: cutting off high-fat diet during intervention and continuing normal diet) and eight non-obese rats (NC: non-obese control group, weight 283.10±42.26 g) were studied. Training protocol included running five days a week on the treadmill for 10 weeks with at intensity of 90% of maximum oxygen uptake. Forty-eight hours after the last intervention session, blood and tissue samples were taken to measure biochemical variables. Data were analyzed using one-way analysis of variance and Kruskal–Wallis tests at a significance level of P≤0.05. Results: No significant difference was observed in the tissue levels of UCP-2 and MCP-1 and plasma levels of insulin among groups. Plasma glucose levels in the OC-1 group was significantly higher than in the NC, OC-2, HIIT, HPD, and HIIT+HPD groups, it was significantly higher in the OC-2, HIIT, HPD and HIIT+HPD groups than the NC group, and it was significantly higher in the HPD group than in the OC-2 group (P≤0.05). Also, insulin sensitivity index was significantly higher in the OC-2 group than in the OC-1, HIIT and HPD groups (P≤0.05). Conclusion: Long periods of using a high-fat diet, although it increases the risk of obesity, may not change the inflammatory state. On the other hand, modifying the diet and doing regular exercise can lead to the improvement of glycemic disorder caused by consuming a high-fat

Keywords

Main Subjects

References

  1. Battineni G, Sagaro GG, Chintalapudi N, Amenta F, Tomassoni D, Tayebati SK. Impact of obesity-induced inflammation on cardiovascular diseases (CVD). International Journal of Molecular Sciences. 2021;22(9):4798.
  2. Spezia M, Bonato A, De Fortunato G, Bossi A, Glauber M. The role of obesity and adipokines in coronary microvascular dysfunction: a systematic review and meta-analysis. European Heart Journal-Cardiovascular Imaging. 2021;22(Supplement_1): 356. 83.
  3. Cheraghpour M, Ehrampoush E, Homayounfar R, Davoodi H, Zand H, Mimmiran P. The relationship between the immune system and the inflammatory mechanisms in obesity with insulin resistance. Nutrition Sciences and Food Technology. 2013;7(5): 723-735. [In Persian]
  4. Basurto L, Gregory MA, Hernández SB, Sánchez-Huerta L, Martínez AD, Manuel-Apolinar L, et al. Monocyte chemoattractant protein-1 (MCP-1) and fibroblast growth factor-21 (FGF-21) as biomarkers of subclinical atherosclerosis in women. Experimental Gerontology. 2019;124:110624.
  5. Lee CH, Lam KS. Obesity‐induced insulin resistance and macrophage infiltration of the adipose tissue: a vicious cycle. Journal of Diabetes Investigation. 2019;10(1):29.
  6. Evers-van Gogh IJ, Oteng A-B, Alex S, Hamers N, Catoire M, Stienstra R, et al. Muscle-specific inflammation induced by MCP-1 overexpression does not affect whole-body insulin sensitivity in mice. Diabetologia. 2016;59:624-33.
  7. Temaru R, Urakaze M, Satou A, Yamazaki K, Nakamura N, Kobayashi M. High glucose enhances the gene expression of interleukin-8 in human endothelial cells, but not in smooth muscle cells: possible role of interleukin-8 in diabetic macroangiopathy. Diabetologia. 1997;40:610-3.
  8. Raschke S, Eckel J. Adipo‐myokines: Two sides of the same coin mediators of inflammation and mediators of exercise. Mediators of Inflammation. 2013;2013(1):320724.
  9. Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe T, Kubota N, et al. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. Journal of Biological Chemistry. 2006;281(36):26602-14.
  10.  Rajasekaran, M., Sul, OJ., Choi, EK., Kim, JE., Suh, J H., & Choi, HS. MCP-1 deficiency enhances browning of adipose tissue via increased M2 polarization. The Journal of  Endocrinology. 2019:242(2), 91–101.
  11. Kristono GA, Holley AS, Hally KE, Brunton-O'Sullivan MM, Shi B, Harding SA, et al. An IL-6-IL-8 score derived from principal component analysis is predictive of adverse outcome in acute myocardial infarction. Cytokine: X. 2020;2(4):100037.
  12. Mao L, Lei J, Schoemaker MH, Ma B, Zhong Y, Lambers TT, et al. Long-chain polyunsaturated fatty acids and extensively hydrolyzed casein-induced browning in a Ucp-1 reporter mouse model of obesity. Food & function. 2018;9(4):2362-73.
  13. Liu Y, Jiang H, He LY, Huang WJ, He X-Y, Xing F-Q. Abnormal expression of uncoupling protein-2 correlates with CYP11A1 expression in polycystic ovary syndrome. Reproduction, Fertility and Development. 2011;23(4):520-6.
  14. Ji F, Shen T, Zou W, Jiao J. UCP2 regulates embryonic neurogenesis via ROS-mediated Yap alternation in the developing neocortex. Stem Cells. 2017;35(6):1479-92.
  15. Boss O. Uncoupling protein-3: a new member of the mitoconndorial carrier family with tissue-specific expression. FEBS Letters. 1997;39:408.
  16. Yu XX, Mao W, Zhong A, Schow P, Brush J, Sherwood S, et al. Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP-4 and UCP-5 expression through dietary or temperature manipulation. FAZEB Journal. 2000;14(11): 1611-1618.
  17. Malli R, Graier WF. The role of mitochondria in the activation/maintenance of SOCE: The contribution of mitochondrial Ca 2+ uptake, mitochondrial motility, and location to store-operated Ca 2+ entry. Advances in Experimental Medicine and Biology. 2017; 993: 297–319.
  18. Kim HJ, Seong JK. UCP2 KO mice exhibit ameliorated obesity and inflammation induced by high-fat diet feeding. BMB Reports. 2022;55(10):500.
  19. Oliveira MS, Rheinheimer J, Moehlecke M, Rodrigues M, Assmann TS, Leitão CB, et al. UCP2, IL18, and miR-133a-3p are dysregulated in subcutaneous adipose tissue of patients with obesity. Molecular and Cellular Endocrinology. 2020;509:110805.
  20. Alivand M, Alipour B, Moradi S, Khaje-Bishak Y, Alipour M. The review of the relationship between UCP2 and obesity: Focusing on inflammatory-obesity. New Insights in Obesity: Genetics and Beyond. 2021;5(1):001-13.
  21. Yuan Z, Xiao-Wei L, Juan W, Xiu-Juan L, Nian-Yun Z, Lei S. HIIT and MICT attenuate high-fat diet-induced hepatic lipid accumulation and ER stress via the PERK-ATF4-CHOP signaling pathway. Journal of Physiology and Biochemistry. 2022;78(3):641-52.
  22. Gonzalez-Gil AM, Elizondo-Montemayor L. The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A Review. Nutrients. 2020;12(6):1899.
  23. Callegari IO, Rocha GZ, Oliveira AG. Physical exercise, health, and disease treatment: The role of macrophages. Frontiers in Physiology. 2023;14:1061353.
  24. Calcaterra V, Vandoni M, Rossi V, Berardo C, Grazi R, Cordaro E, et al. Use of physical activity and exercise to reduce inflammation in children and adolescents with obesity. International Journal of Environmental Research and Public Health. 2022;19(11):6908.
  25. Rajar HA, Hashmi MA, Akhtar S, Amin U, John A. The effect of high intensity interval training in reducing the risk of cardiovascular diseases in obese type-I individuals. Allied Medical Research Journal. 2023;1(2):86-95.
  26. Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity‐related inflammation and insulin resistance: cells, cytokines, and chemokines. International Scholarly Research Notices. 2013;2013(1):139239.
  27. Kazemi A. Effect of high intensity interval training on visceral and subcutaneous levels of MCP-1 and plasma insulin and glucose in male rats. Razi Journal of Medical Science. 2017; 23(152): 29-37. [In Persian]
  28. Mofrad SRN, Golpasandi H, Sakhaei MH, Khalafi M. The effect of high intensity interval training on inflammatory markers in patient with type 2 diabetes: a systematic review and meta-analysis. Journal of Applied Health Studies in Sport Physiology. 2022;9(2):123-37. [In Persian]
  29. Kalantar-Zadeh K, Kramer HM, Fouque D. High-protein diet is bad for kidney health: unleashing the taboo. Nephrology Dialysis Transplantation, 2020; 35(1): 1-4.‏
  30. Jiang S, Ji S, Tang X, Wang T, Wang H, Meng X. A comparison study on the therapeutic effect of high protein diets based on pork protein versus soybean protein on obese mice. Foods. 2022;11(9):1227.
  31. Song S, Gao Y, Xia T, Zhou Y, Hooiveld GJ, Muller M, et al. Effects of high dietary chicken protein on obesity development of rats fed high-fat diets. Journal of Functional Foods. 2023;108:105713.
  32. Pivovarova-Ramich O, Markova M, Weber D, Sucher S, Hornemann S, Rudovich N, et al. Effects of diets high in animal or plant protein on oxidative stress in individuals with type 2 diabetes: A randomized clinical trial. Redox Biology. 2020;29:101397.
  33. De Carvalho FG, Justice JN, Freitas ECd, Kershaw EE, Sparks LM. Adipose tissue quality in aging: how structural and functional aspects of adipose tissue impact skeletal muscle quality. Nutrients. 2019;11(11):2553.
  34. Mu W-J, Zhu J-Y, Chen M, Guo L. Exercise-mediated browning of white adipose tissue: its significance, mechanism and effectiveness. International Journal of Molecular Sciences. 2021;22(21):11512.
  35. Križančić Bombek L, Čater M. Skeletal Muscle Uncoupling Proteins in Mice Models of Obesity. Metabolites. 2022;12(3):259.
  36. Ropelle ER, Pauli JR, Fernandes MFA, Rocco SA, Marin RM, Morari J, et al. A central role for neuronal AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in high-protein diet–induced weight loss. Diabetes. 2008;57(3):594-605.
  37. Kawanishi N, Takagi K, Lee H-C, Nakano D, Okuno T, Yokomizo T, et al. Endurance exercise training and high-fat diet differentially affect composition of diacylglycerol molecular species in rat skeletal muscle. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2018;314(6):R892-R901.
  38. Lee J-J, Kim HA, Lee J. The effects of Brassica juncea L. leaf extract on obesity and lipid profiles of rats fed a high-fat/high-cholesterol diet. Nutrition Research and Practice. 2018;12(4):298.
  39. Jamali E, Asad MR, Rassouli A. The effect of high-intensity interval training (HIIT) on resistin gene expression in visceral adipose tissue in obese male rats. International Journal of Applied Exercise Physiology. 2016;5(1): 2322-3537.
  40. Høydal MA, Wisløff U, Kemi OJ, Ellingsen Ø. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. European Journal of Preventive Cardiology. 2007;14(6):753-60.
  41. Sanchez J. Insulin Sensitivity. Encyclopedia of Behavioral Medicine: Springer; 2020. 1201-1202.
  42. Supriya R, Delfan M, Saeidi A, Samaie SS, Al Kiyumi MH, Escobar KA, et al. Spirulina supplementation with high-intensity interval training decreases adipokines levels and cardiovascular risk factors in men with obesity. Nutrients. 2023;15(23):4891.
  43. Medeiros CS, de Sousa Neto IV, Silva KKS, Cantuária APC, Rezende TMB, Franco OL, et al. The effects of high-protein diet and resistance training on glucose control and inflammatory profile of visceral adipose tissue in rats. Nutrients. 2021;13(6):1969.
  44. Stenkula KG, Erlanson-Albertsson C. Adipose cell size: importance in health and disease. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2018;315(2):R284-R95.
  45. Riyahi V, Morovvati H, Khosravi A. The effect of 12 weeks of aerobic training on the function of beta cells and uncoupled protein 2 pancreas of diabetic obese rats. Journal of Applied Health Studies in Sport Physiology. 2023;10(1):141-53. [In Persian]
  46. Shirvani H, Rahmati-Ahmadabad S. The combined effect of high intensity interval training and flaxseed oil supplement on cardioprotection: by UCP2, UCP3 and eNOS mRNA expression. Journal of Mazandaran University of Medical Sciences. 2018;28(160):8-18. [In Persian]
  47. Ryu V, Watts AG, Xue B, Bartness TJ. Bidirectional crosstalk between the sensory and sympathetic motor systems innervating brown and white adipose tissue in male Siberian hamsters. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2017;312(3):R324-R37.
  48. Lagzdina R, Rumaka M, Gersone G, Tretjakovs P. Circulating levels of IL-8 and MCP-1 in healthy adults: changes after an acute aerobic exercise and association with body composition and energy metabolism. International Journal of Molecular Sciences. 2023;24(19):14725.
  49. Peymani M, Ghaedi K, Irani S, Nasr-Esfahani MH. Peroxisome proliferator-activated receptor γ activity is required for appropriate cardiomyocyte differentiation. Cell Journal (Yakhteh). 2016;18(2):221. [In Persian]
  50. Pierelli G, Stanzione R, Forte M, Migliarino S, Perelli M, Volpe M, et al. Uncoupling protein 2: a key player and a potential therapeutic target in vascular diseases. Oxidative Medicine and Cellular Longevity. 2017;2017(1):7348372.
  51. Nedergaard J, Golozoubova V, Matthias A, Asadi A, Jacobsson A, Cannon B. UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2001;1504(1):82-106.
  52. Wu MV, Bikopoulos G, Hung S, Ceddia RB. Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats: impact on whole-body energy expenditure. Journal of Biological Chemistry. 2014;289(49):34129-40.
  53. Koch C, Lowe C, Pretz D, Steger J, Williams L, Tups A. High‐fat diet induces leptin resistance in leptin‐deficient mice. Journal of Neuroendocrinology. 2014;26(2):58-67.
  54. Tsukita S, Yamada T, Uno K, Takahashi K, Kaneko K, Ishigaki Y, et al. Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals. Cell Metabolism. 2012;16(6):825-32.
  55. Rasyid H, Aman M, Lawrence GS. High-fat diet increases the level of circulating monocyte chemoattractant protein-1 in Wistar rats, independent of obesity. Annals of Medicine and Surgery. 2021;65.
  56. Decleves A-E, Mathew AV, Cunard R, Sharma K. AMPK mediates the initiation of kidney disease induced by a high-fat diet. Journal of the American Society of Nephrology. 2011;22(10):1846-55.
  57. Wang N, Guo J, Liu F, Wang M, Li C, Jia L, et al. Depot-specific inflammation with decreased expression of ATM2 in white adipose tissues induced by high-margarine/lard intake. PLoS One. 2017;12(11):e0188007.
  58. Maharjan BR, McLennan SV, Yee C, Twigg SM, Williams PF. The effect of a sustained high-fat diet on the metabolism of white and brown adipose tissue and its impact on insulin resistance: A selected time point cross-sectional study. International Journal of Molecular Sciences. 2021;22(24):13639.
  59. Vidal P, Baer LA, Félix-Soriano E, Yang FT, Branch DA, Baskin KK, et al. Distinct effects of high-fat and high-phosphate diet on glucose metabolism and the response to voluntary exercise in male mice. Nutrients. 2022;14(6):1201.
  60. Magalhães A, Barra C, Borges A, Santos L. Diet Modifications towards Restoration of Insulin Sensitivity and Daily Insulin Fluctuations in Diabetes. Diabetology. 2022;3(4):606-14.
  61. Jalo A, Helin JS, Hentilä J, Nissinen TA, Honkala SM, Heiskanen MA, et al. Mechanisms leading to increased insulin-stimulated cerebral glucose uptake in obesity and insulin resistance: A high-fat diet and exercise training intervention PET study with rats (CROSRAT). Journal of Functional Morphology and Kinesiology. 2024;9(2):58.
Journal of Applied Health Studies in Sport Physiology
Volume 12, Issue 2
August 2025
Pages 75-88

Files

History

  • Receive Date: 17 July 2024
  • Revise Date: 16 November 2024
  • Accept Date: 16 November 2024

Share

How to cite

Statistics