The Effect of High Intensity Interval Training on Lipocalin 2 Gene Expression in Subcutaneous Adipose Tissue and Insulin Function in Obese Rats with Induced Diabetes

Document Type : Research Paper


1 Ph.D Student of Exercise Physiology, Islamic Azad University, Islamshahr Branch, Tehran, Iran.

2 Assistant Professor of Exercise Physiology, Islamshahr Branch, Islamic Azad University, Tehran, Iran.

3 Assistant Professor of Exercise Physiology, Saveh Branch, Islamic Azad University, Saveh, Iran.

4 Assistant Professor, Department of Physical Education and Sports Sciences, Parand Branch, Islamic Azad University, Tehran, Iran.


Introduction: Genetic evidence indicates the key role of transcription factors on insulin signaling pathways. The present study was performed with the aim of assess the effect of high intensity interval training (HIIT) on gene lipocalin-2 (LCP2) gene expression in subcutaneous adipose tissue, insulin resistance and glucose in obese rats with type 2 diabetic (T2D). Methods: For this purpose, 21 male Wistar rats aged 10 weeks of old were obesed by 8 weeks high-fat diet (HFD) and then 14 rats became T2D by STZ injection (25 mg/dL). The rats were divided into obese, control diabetic and HIIT diabetic groups. HIIT group participated in 8-week HIIT (5 sessions/weekly), and the control groups did not participate in the exercise program. 48 hours after the last training session, glucose and insulin resistance and gene LCN2 expression in subcutaneous adipose tissue were measured and compared by one-way ANOVA test. Results: Type 2 diabetes induction led to an increase in glucose and insulin resistance (P=0.001) as well as an increase in the expression of LCN2 (P=0.001) compared to the obese group. In other words, HIIT led to a significant decrease in glucose, insulin resistance (P=0.001) as well as a significant decrease in LCN2 expression (P=0.002) in subcutaneous adipose tissue compared to the diabetic control group. Conclusion: HIIT is associated with improvement of insulin resistance and glycemic profile in diabetic rats, and this can be imputed to the increase in LCN2 expression in subcutaneous adipose tissue in response to HIIT.


Main Subjects

  1. Amine Ikhanjal M, Ali Elouarid M, Zouine C, Alami H, Errafii K, Ghazal H, et al. FTO gene variants (rs9939609, rs8050136 and rs17817449) and type 2 diabetes mellitus risk: A Meta-Analysis. Gene. 2023 Dec 15; 887:147791.
  2. Peña A, Olson ML, Ayers SL, Sears DD, Vega-López S, Colburn AT, Shaibi GQ. Inflammatory Mediators and Type 2 Diabetes Risk Factors before and in Response to Lifestyle Intervention among Latino Adolescents with Obesity. Nutrients. 2023 May 24; 15(11):2442.
  3. Wang Y, Lam KSL, Kraegen EW. Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans, Clin Chem, 2007; 53(1):34-41.
  4. Esteve E, Ricart W, and Fernandez-Real JM. Adipocytokines and insulin resistance: the possible role of lipocalin-2, retinol binding protein-4, and adiponectin, Diabetes Care, 2009; 32(2): 362-7.
  5. Jaberi SA, Cohen A, D'Souza C, Abdulrazzaq YM, Ojha S, Bastaki S, Adeghate EA. Lipocalin-2: Structure, function, distribution and role in metabolic disorders. Biomed Pharmacother. 2021 Oct; 142:112002.
  6. Cowland JB, Muta T, Borregaard N. IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is controlled by IkappaB-zeta. J Immunol 2006; 176: 5559-66.
  7. Shen F, Hu Z, Goswami J, Gaffen SL. Identification of common transcriptional regulatory elements in interleukin17 target genes. J Biol Chem 2006; 281: 24138-48.
  8. Schinzari F, Vizioli G, Campia U, Cardillo C, Tesauro M. Variable dysregulation of circulating lipocalin-2 in different obese phenotypes: Association with vasodilator dysfunction. Vasc Med. 2023 Aug; 28(4):266-273.
  9. Takaya J, Tanabe Y, Kaneko K. Increased lipocalin 2 levels in adolescents with type 2 diabetes mellitus. J Pediatr Endocrinol Metab. 2021 Jun 14; 34(8):979-985.
  10. Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, Tso AW, et al. Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem 2007; 53: 34-41.
  11. Zhang W, Chen S, Zhuang X. Research Progress on Lipocalin-2 in Diabetic Encephalopathy. Neuroscience. 2023 Apr 1; 515:74-82.
  12. Choi KM, Kim TN, Yoo HJ. Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women, Clin Endocrin, 2009; 70:569-74.
  13. Moghadasi M, Mohammadi Domieh A. Effects of Resistance versus Endurance Training on Plasma Lipocalin-2 in Young Men. Asian J Sports Med 2014; 5(2): 108-114.
  14. Mohammadi Domieh A, Khajehlandi A. Lipocalin-2: Response to Resistance Training in Obese Young Men. Intl j Sport Std 2014; 4(4): 458-461.
  15. Van Dam RM, Hu FB. Lipocalins and insulin resistance: etiological role of retinol-binding protein 4 and lipocalin-2? Clin Chem 2007; 53: 5-7.
  16. Moghadasi M, Mohammadi Domieh A. Effects of Resistance versus Endurance Training on Plasma Lipocalin-2 in Young Men. Asian J Sports Med. 2014 Jun; 5(2):108-14.
  17. Atashak S, Stannard SR, Daraei A, Soltani M, Saeidi A, Moradi F, Laher I, Hackney AC, Zouhal H. High-intensity Interval Training Improves Lipocalin-2 and Omentin-1 Levels in Men with Obesity. Int J Sports Med. 2022 Apr; 43(4):328-335.
  18. Parker L, Ang T, Morrison DJ, Lee NJ, Levinger I, Keske MA. Prior aerobic exercise mitigates the decrease in serum osteoglycin and lipocalin-2 following high-glucose mixed-nutrient meal ingestion in young men. Am J Physiol Endocrinol Metab. 2022 Sep 1; 323(3):319-332.
  19. Sabzevari F, Mogharnasi M, Golestani F. Effect of 6 weeks Pilates training along with dill supplementation on serum concentrations of nesfatin-1, lipocalin-2, and insulin resistance in females with overweight and obesity: A randomized controlled trial. J Res Med Sci. 2022 Aug 27; 27:59.
  20. Eizadi M, Mirakhori Zahra, Farajtabar Behrestaq S. Effect of 8-Week Interval Training on Protein Tyrosine Phosphatase 1B Expression in Gastrocnemius Muscle and Insulin Resistance in Rats with Type 2 Diabetes. Avicenna J Med Biochem. 2019; 7(2): 51-56.
  21. Marita AR, Sarkar JA, Rane S. Type 2 diabetes in non-obese Indian subjects is associated with reduced leptin levels: Study from Mumbai, Western India. Molecular and Cellular Biochemistry. 2005; 275: 143–151.
  22. Lopes FL, Desmarais J, Gevry NY, Ledoux S, Murphy BD. Expression of vascular endothelial growth factor isoforms and receptors Flt-1 and KDR during the peri-implantation period in the mink, Mustela vison. Biol Reprod. 2003; 68(5):1926-33.
  23. Maltais ML, Perreault K, Courchesne-Loyer A, Lagacé JC, Barsalani R, Dionne IJ. 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. Int J Sport Nutr Exerc Metab. 2016 Feb; 26(1):71-7.
  24. Vancea DM, Vancea JN, Pires MI, Reis MA, Moura RB, Dib SA. Effect of frequency of physical exercise on glycemic control and body composition in type 2 diabetic patients. Arq Bras Cardiol. 2009; 92(1):23-30.
  25. Eizadi M, Ravasi AA, Soori R, Baesi K, Choubineh S. Effect of three months aerobic training on TCF7L2 expression in pancreatic tissue in type 2 diabet es rats induced by streptozotocin- nicotinamide. Feyz 2017; 21(1): 1-8.
  26. Moghadasi M, Mohammadi Domieh A. Effects of Resistance versus Endurance Training on Plasma Lipocalin-2 in Young Men. Asian J Sports Med. 2014 Jun; 5(2):108-14.
  27. Talebi-garakani E, Hoseini-Andargoli M, Fathi R, Safarzade A R. 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. 2012; 14 (2): 178-184.
  28. Atashak S, Ahmadi-Zad A.Effect of eight weeks of resistance exercise on new biomarkers of cardiovascular disease in obese adult males. Feyz 2017; 21(3): 256-64.
  29. Guo H, Jin D, Chen X. Lipocalin 2 is a regulator of macrophage polarization and NF-κB/STAT3 pathway activation. Molecular Endocrinology. 2014, 28(10):1616-28.
  30. Wei N. Role of Lipocalin-2 in Brain Injury after Intra cerebral Hemorrhage. Journal of Cerebral Blood Flow & Metabolism Official Journal of the International Society of Cerebral Blood Flow & Metabolism. 2015, 35(9):1454.
  31. Sommer G, Weise S, Kralisch S. Lipocalin-2 is induced by interleukin-1β in murine adipocytes in vitro, J Cell Biochemistry, 2009; 106:103-8.
  32. Mehrabai J, Damirchi M, Rahmaninia F. Effect of Two Aerobic Exercise Intensities on Lipocalin-2, Interleukin-1ß Levels, and Insulin Resistance Index in Sedentary Obese Men. Sport Physiology. 2014; 6(21): 10-95.
  33. Zhao P, Elks CM, Stephens JM. The induction of lipocalin-2 expression in vivo and in vitro. J Biol Chem.2014; 289(9): 5960-9.
  34. Zhang J, Wu Y, Zhang Y, Leroith D, Bernlohr DA, Chen X. The role lipocalin 2 in the regulation of inflammation in adipocytes and macrophages. Mol Endocrinol.2008; 22(6): 1416-26.
  35. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell.2002; 10(5): 1033-43.
Volume 12, Issue 2
June 2024
Pages 82-89
  • Receive Date: 31 October 2023
  • Revise Date: 01 December 2023
  • Accept Date: 13 December 2023