Improvement of glycemic profile following resistance training in diabetic rats with emphasis on lipocalin 2 expression

Subject Areas : Journal of Animal Biology

Mohammad Pakray ¹ , Shahram Soheily ²

1 - Department of Physical Education and Sport Sciences, Shahr-e-Qods Branch, Islamic Azad University, Tehran, Iran
2 - Department of Physical Education and Sport Sciences, Shahr-e-Qods Branch, Islamic Azad University, Tehran, Iran

Received: 2024-05-01 Accepted : 2024-08-06 Published : 2025-01-13

Keywords: Resistance training, Lipocalin-2 gene expression, Insulin resistance, Glycemic profile, Type 2 diabetes,

Abstract :

Lipocalin-2 has been introduced as one of the most important inflammatory mediators related to obesity and effective in glucose homeostasis. The purpose of this study was to determine the effect of resistance training on lipocalin 2 gene expression in subcutaneous adipose tissue as well as glycemic profile in obese diabetic rats. 14 male Wistar rats were divided into control and resistance training groups after induction of type 2 diabetes by high-fat diet and STZ injection. Resistance exercises were performed for 6 weeks, 5 sessions per week, in the form of climbing a step ladder by the rats of the resistance group. 48 hours after the last training session, all rats were dissected. Lipocalin 2 gene expression, glucose, glycosylated hemoglobin and insulin resistance were measured and compared between two groups by independent t-test. Compared to the control group, resistance training resulted in a significant decrease in glucose (P = 0.001), glycosylated hemoglobin (P = 0.016), insulin resistance (P = 0.001) and lipocalin 2 gene expression in subcutaneous fat tissue (P = 0.003) and as well as a significant increase in serum insulin (P = 0.042). Based on these findings, the improvement of the glycemic profile in the studied rats may be attributed to the decrease in the expression of lipocalin-2 and insulin resistance following resistance training. Further studies are needed to better understand the mechanisms responsible for these changes.

References:

1. Lopes W.A., Leite N., da Silv, L.R., Brunelli D.T., Gáspari A.F., Radominski R. B., Chacon-Mikahil, M.P., & Cavaglieri C.R. 2016. Effects of 12 weeks of combined training without caloric restriction on inflammatory markers in overweight girls. Journal of sports sciences, 34(20), 1902–1912.
2. Alibegovic A.C., Sonne M.P., Højbjerre L., Hansen T., Pedersen O., van Hall G., Holst J. J., Stallknecht B., Dela F., & Vaag A. 2010. The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest. Diabetes, 59(4), 836–843.
3. Atashak S., Ahmadi-Zad A. 2017. Effect of eight weeks of resistance exercise on new biomarkers of cardiovascular disease in obese adult males. Feyz, 21(3): 256-64.
4. Choi K.M., Kim T.N., Yoo H.J. 2009. Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women, Clin Endocrin, 70:569-74.
5. Cowland, J.B., Muta, T., & Borregaard, N. 2006. IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is controlled by IkappaB-zeta. Journal of immunology Baltimore, Md, 1950, 176(9), 5559–5566.
6. Eizadi M., Soory R., Ravasi A., Baesy, K., Choobineh S. 2017. Relationship between TCF7L2 Relative Expressions in Pancreas Tissue with Changes in Insulin by High Intensity Interval Training (HIIT) in Type 2 Diabetes Rats, JSSU, 24(12):981-993.
7. Esteve E., Ricart W., & Fernández-Real J.M. 2009. Adipocytokines and insulin resistance: the possible role of lipocalin-2, retinol binding protein-4, and adiponectin. Diabetes care, 32 (2), S362–S367.
8. Fain J.N. 2006. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitamins and hormones, 74, 443–477.
9. Ferreira A.C., Dá Mesquita S., Sousa J. C., Correia-Neves M., Sousa N., Palha J. A., & Marques F. 2015. From the periphery to the brain: Lipocalin-2, a friend or foe? Progress in Neurobiology, 131, 120–136.
10. Ford E.S. 2005. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S. Diabetes care, 28(11), 2745–2749.
11. Glans F., Eriksson K.F., Segerström A., Thorsson O., Wollmer P., & Groop L. 2009. Evaluation of the effects of exercise on insulin sensitivity in Arabian and Swedish women with type 2 diabetes. Diabetes research and clinical practice, 85(1), 69–74.
12. Goetz D.H., Holmes M.A., Borregaard N., Bluhm M. E., Raymond K.N., & Strong R.K. 2002. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Molecular cell, 10(5), 1033–1043.
13. Jager J., Grémeaux T., Cormont M., Le Marchand-Brustel Y., & Tanti J.F. 2007. Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology, 148(1), 241–251.
14. Jayaraman A., Roberts K.A., Yoon J., Yarmush D.M., Duan X., Lee K., & Yarmush M.L. 2005. Identification of neutrophil gelatinase-associated lipocalin (NGAL) as a discriminatory marker of the hepatocyte-secreted protein response to IL-1beta: a proteomic analysis. Biotechnology and bioengineering, 91(4), 502–515.
15. Jessen B.A., & Stevens G.J. 2002. Expression profiling during adipocyte differentiation of 3T3-L1 fibroblasts. Gene, 299(1-2), 95–100.
16. Klöting N., Schleinitz D., Ruschke K., Berndt J., Fasshauer M., Tönjes A., Schön M.R., Kovacs P., Stumvoll M., & Blüher, M. 2008. Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humans. Diabetologia, 51(4), 641–647.
17. Leonardini A., Laviola L., Perrini S., Natalicchio A., Giorgino F. 2009. Cross-Talk between PPARgamma and Insulin Signaling and Modulation of Insulin Sensitivity. PPAR Res, 2009:818945.
18. Lopes W.A., Leite N., da Silva L.R., Brunelli D.T., Gáspari A.F., Radominski R.B., Chacon-Mikahil M.P., & Cavaglieri, C.R. 2016. Effects of 12 weeks of combined training without caloric restriction on inflammatory markers in overweight girls. Journal of sports sciences, 34(20), 1902–1912.
19. Maltais M.L., Perreault K., Courchesne-Loyer A., Lagacé J.C., Barsalani R., & Dionne I.J. 2016. Effect of Resistance Training and Various Sources of Protein Supplementation on Body Fat Mass and Metabolic Profile in Sarcopenic Overweight Older Adult Men: A Pilot Study. International journal of sport nutrition and exercise metabolism, 26(1), 71–77.
20. McAuley K.A., Williams S.M., Mann J.I., Walker R.J., Lewis-Barned N.J., Temple L.A., & Duncan A.W. 2001. Diagnosing insulin resistance in the general population. Diabetes care, 24(3), 460–464.
21. Mehrabani J., Damirchi2 A., & Rahmaninia F. 2014. Effect of Two Aerobic Exercise Intensities on Lipocalin-2, Interleukin-1ß Levels, and Insulin Resistance Index in Sedentary Obese Men. Sport Physiology, 6(21), 95-108.
22. Moghadasi M., Mohammadi D.A. 2014. Effects of Resistance versus Endurance Training on Plasma Lipocalin-2 in Young Men. Asian journal of sports medicine, 5(2), 108–114.
23. Moghadasi M., Mohammadi Domieh A. 2014. Effects of Resistance versus Endurance Training on Plasma Lipocalin-2 in Young Men. Asian journal of sports medicine, 5(2), 108–114.
24. Oliveira C.A., Paiva M.F., Mota C. A., Ribeiro C., Leme J.A., Luciano E., & Mello M. A.,2010. Exercise at anaerobic threshold intensity and insulin secretion by isolated pancreatic islets of rats. Islets, 2(4), 240–246.
25. Oliveira C.A., Paiva M.F., Mota C. A., Ribeiro C., Leme J.A., Luciano E., & Mello M.A. 2010. Exercise at anaerobic threshold intensity and insulin secretion by isolated pancreatic islets of rats. Islets, 2(4), 240–246.
26. Shen F., Hu Z., Goswami J., & Gaffen, S.L. 2006. Identification of common transcriptional regulatory elements in interleukin-17 target genes. The Journal of biological chemistry, 281(34), 24138–24148.
27. Sommer G., Weise S., Kralisch S., Lossner U., Bluher M., Stumvoll M., & Fasshauer M. 2009. Lipocalin-2 is induced by interleukin-1beta in murine adipocytes in vitro. Journal of cellular biochemistry, 106(1), 103–108.
28. Park S., Hong S.M., Lee J. E., & Sung S.R. 2007. Exercise improves glucose homeostasis that has been impaired by a high-fat diet by potentiating pancreatic beta-cell function and mass through IRS2 in diabetic rats. Journal of applied physiology (Bethesda, Md.: 1985), 103(5), 1764–1771.
29. Talebi-garakani E., Hoseini-Andargoli M., Fathi R., Safarzade A.R. 2012. Changes of Adipose Tissue Lipocalin-2 gene Expression in Response to One Session Exercise in the Streptozotocin-Induced Diabetic Rats. Iranian Journal of Endocrinology and Metabolism, 14(2): 178-184.
30. Tontonoz P., & Spiegelman B.M. 2008. Fat and beyond: the diverse biology of PPARgamma. Annual Review of biochemistry, 77, 289–312.
31. Van Dam R.M., & Hu F.B. 2007. Lipocalins and insulin resistance: etiological role of retinol-binding protein 4 and lipocalin-2. Clinical chemistry, 53(1), 5–7.
32. Vancea D. M., Vancea J.N., Pires M. I., Reis M.A., Moura R.B., & Dib S.A. 2009. Effect of frequency of physical exercise on glycemic control and body composition in type 2 diabetic patients. Arquivos brasileiros de cardiologia, 92(1), 23–30.
33. Wang Y., Lam K.S., Kraegen E.W., Sweeney G., Zhang J., Tso A.W., Chow W.S., Wat N.M., Xu J.Y., Hoo R.L., & Xu A. 2007. Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clinical chemistry, 53(1), 34–41.
34. Ni W., Zheng M., Xi G., Keep R.F., & Hua Y. 2015. Role of lipocalin-2 in brain injury after intracerebral hemorrhage. Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism, 35(9), 1454–1461.
35. Yazdanpazhooh S., Banaeifar A., Arshadi S., Eizadi M. 2019. The effect of resistance training on PPARy expression in subcutaneous fat tissue of diabetic rats with high fat diet and STZ. Razi Journal of Medical Sciences, 26(8):68-77.
36. Zhang J., Wu Y., Zhang Y., Leroith D., Bernlohr D.A., & Chen X. 2008. The role of lipocalin 2 in the regulation of inflammation in adipocytes and macrophages. Molecular endocrinology (Baltimore, Md.), 22(6), 1416–1426.
37. Zhao P., Elks C.M., & Stephens J.M. 2014. The induction of lipocalin-2 protein expression in vivo and in vitro. The Journal of biological chemistry, 289(9), 5960–5969.