Journal of Eexercise & Organ Cross Talk

Impact of high-intensity interval training on ASC inflammasome, lipid profile and their correlation in diabetic rat model

Document Type : Original Article

Authors

1 Department of sport physiology, Faculty of sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

2 Department of Basic Sciences, Division of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

3 Stem Cells and Transgenic Technology Research Center, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

Abstract
In Diabetes (Di) exercise training especially high-intensity interval training (HIIT) reduce blood lipids and improve anti-inflammatory status. In this study, we aimed to investigate the impact of high-intensity interval training on ASC inflammasome, lipid profile, and their correlation in diabetic rat models. Twenty rats were divided into four groups, including a control group, HIIT, Di, and Di+HIIT (n=5 in each group). Diabetes was induced using a combination of a high-fat diet (HFD) and STZ. Wistar rats in the exercise groups were subjected to high-intensity interval training for eight weeks. After sample collection, liver tissue was removed and weighed. Serum levels of lipid profile were measured by special kit. Protein expression of the apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) in liver tissue was determined by Western blot. The results of the present study showed that diabetes induction significantly increased LDL, cholesterol, triglyceride and ASC levels and decreased HDL levels (p<0.05), whereas HIIT exercise training with diabetes somewhat adjusted the lipid profile and decreased the ASC inflammasome levels (p<0.05). In the correlation analysis, only the correlation between ASC and triglycerides was confirmed in the Di+HIIT group (p=0.043, r=0.997). Diabetes induction adversely affects lipid profiles and increases ASC inflammasome levels. However, high-intensity interval training (HIIT) appears to mitigate these effects by improving the lipid profile and reducing ASC levels. Notably, a significant positive correlation between ASC and triglycerides was observed in the diabetic rats undergoing HIIT, suggesting a link between inflammation and lipid metabolism.

What is already known on this subject?

The role of inflammation and inflammasomes in the pathophysiology and progression of diabetes mellitus (DM), which includes both type 1 (T1D) and type 2 (T2D), is crucial.

 

What this study adds?

the implementation of HIIT in diabetic subjects appears to positively influence these lipid parameters and reduce ASC inflammasome levels.  

Keywords

Subjects


Acknowledgements

None.

Funding

No sources of funding were sought or awarded for this study.

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict of interest.

Ethical approval The ethical code for animal care (EE.1401.2.24.173155) from Ahvaz University approved all phases of the experiment.

Informed consent Animal study.

Author contributions

Conceptualization: R.Sh., S.Sh., M.R.T.; Methodology: R.Sh., S.Sh., M.R.T.; Software: R.Sh.; Validation: S.Sh., Formal analysis; Investigation: M.R.T.; Resources: R.Sh., S.Sh., M.R.T.; Data curation: M.R.T.; Writing - original draft: R.Sh.; Writing – review & editing: R.Sh., S.Sh., M.R.T.; Visualization: R.Sh., S.Sh., M.R.T.; Supervision: S.Sh. Project administration: R.Sh.; Funding acquisition: S.Sh.

Athyros, V. G., Doumas, M., Imprialos, K. P., Stavropoulos, K., Georgianou, E., Katsimardou, A., & Karagiannis, A. (2018). Diabetes and lipid metabolism. Hormones, 17, 61-67. doi: https://doi.org/10.1007/s42000-018-0014-8
Charles, M. A., & Leslie, R. D. (2021). Diabetes: concepts of β-cell organ dysfunction and failure would lead to earlier diagnoses and prevention. Diabetes, 70(11), 2444-2456. doi: https://doi.org/10.2337/dbi21-0012
Dixit, V. D. (2012). Nlrp3 inflammasome activation in type 2 diabetes: is it clinically relevant? Diabetes, 62(1), 22. doi: https://doi.org/10.2337/db12-1115
Feingold, K. R., & Grunfeld, C. (2023). Diabetes and dyslipidemia. In Diabetes And Cardiovascular Disease (pp. 425-472). Springer. doi: https://doi.org/10.1007/978-3-031-13177-6_14
Feng, J., Zhang, Q., Chen, B., Chen, J., Wang, W., Hu, Y., . . . Huang, H. (2024). Effects of high-intensity intermittent exercise on glucose and lipid metabolism in type 2 diabetes patients: a systematic review and meta-analysis. Frontiers in Endocrinology, 15, 1360998. doi: https://doi.org/10.3389/fendo.2024.1360998
Gora, I. M., Ciechanowska, A., & Ladyzynski, P. (2021). NLRP3 inflammasome at the interface of inflammation, endothelial dysfunction, and type 2 diabetes. Cells, 10(2), 314. doi: https://doi.org/10.3390/cells10020314
Grant, R. W., & Dixit, V. D. (2013). Mechanisms of disease: inflammasome activation and the development of type 2 diabetes. Frontiers in immunology, 4, 50. doi: https://doi.org/10.3389/fimmu.2013.00050
Jelleyman, C., Yates, T., O'Donovan, G., Gray, L. J., King, J. A., Khunti, K., & Davies, M. J. (2015). The effects of high‐intensity interval training on glucose regulation and insulin resistance: a meta‐analysis. Obesity Reviews, 16(11), 942-961. doi: https://doi.org/10.1111/obr.12317
Kanaley, J. A., Colberg, S. R., Corcoran, M. H., Malin, S. K., Rodriguez, N. R., Crespo, C. J., . . . Zierath, J. R. (2022). Exercise/physical activity in individuals with type 2 diabetes: a consensus statement from the American College of Sports Medicine. Medicine and science in sports and exercise, 54(2), 353. doi: https://doi.org/10.1249/MSS.0000000000002800
Keating, S. E., Hackett, D. A., Parker, H. M., O’Connor, H. T., Gerofi, J. A., Sainsbury, A., . . . George, J. (2015). Effect of aerobic exercise training dose on liver fat and visceral adiposity. Journal of hepatology, 63(1), 174-182. doi: https://doi.org/10.1016/j.jhep.2015.02.022
Kim, H., Lee, D. S., An, T. H., Park, H.-J., Kim, W. K., Bae, K.-H., & Oh, K.-J. (2021). Metabolic spectrum of liver failure in type 2 diabetes and obesity: from NAFLD to NASH to HCC. International journal of molecular sciences, 22(9), 4495. doi: https://doi.org/10.3390/ijms22094495
Leandro, C. G., Levada, A. C., Hirabara, S. M., MANHAS-DE-CASTRO, R., De-Castro, C. B., Curi, R., & Pithon-Curi, T. C. (2007). Aprogram of moderate physical training for wistar rats based on maximal oxygen consumption. The Journal of Strength & Conditioning Research, 21(3), 751-756.
Li, Q., Zhao, Z., Si, K., Zhou, J., Liu, H., & Lin, R. (2021). Correlation between the levels of NLRP3, Hcy, IL-1β, IL-18 and the prognosis in patients with hemorrhagic stroke. American Journal of Translational Research, 13(4), 2883. URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC8129339/
Liang, F., Huang, T., Li, B., Zhao, Y., Zhang, X., & Xu, B. (2020). High-intensity interval training and moderate-intensity continuous training alleviate β-amyloid deposition by inhibiting NLRP3 inflammasome activation in APPswe/PS1dE9 mice. Neuroreport, 31(5), 425-432. doi: https://doi.org/10.1097/WNR.0000000000001429
Lindfors, A., Strandberg, R., & Hagström, H. (2025). Screening for advanced liver fibrosis due to metabolic dysfunction-associated steatotic liver disease alongside retina scanning in people with type 2 diabetes: a cross-sectional study. The lancet gastroenterology & hepatology, 10(2), 125-137.
Liu, J., Jia, S., Yang, Y., Piao, L., Wang, Z., Jin, Z., & Bai, L. (2023). Exercise induced meteorin-like protects chondrocytes against inflammation and pyroptosis in osteoarthritis by inhibiting PI3K/Akt/NF-κB and NLRP3/caspase-1/GSDMD signaling. Biomedicine & Pharmacotherapy, 158, 114118. doi: https://doi.org/10.1016/j.biopha.2022.114118
Lu, S., Li, Y., Qian, Z., Zhao, T., Feng, Z., Weng, X., & Yu, L. (2023). Role of the inflammasome in insulin resistance and type 2 diabetes mellitus. Frontiers in immunology, 14, 1052756. doi: https://doi.org/10.3389/fimmu.2023.1052756
 
Mallet, V., Parlati, L., Martinino, A., Pereira, J. P. S., Jimenez, C. N., Sakka, M., . . . Meritet, J.-F. (2022). Burden of liver disease progression in hospitalized patients with type 2 diabetes mellitus. Journal of hepatology, 76(2), 265-274. doi: https://doi.org/10.1016/j.jhep.2021.09.030
Mateo-Gallego, R., Madinaveitia-Nisarre, L., Giné-Gonzalez, J., Bea, A. M., Guerra-Torrecilla, L., Baila-Rueda, L., . . . Lamiquiz-Moneo, I. (2022). The effects of high-intensity interval training on glucose metabolism, cardiorespiratory fitness and weight control in subjects with diabetes: Systematic review a meta-analysis. Diabetes research and clinical practice, 190, 109979. doi: https://doi.org/10.1016/j.diabres.2022.109979
Menini, S., Iacobini, C., Vitale, M., & Pugliese, G. (2020). The inflammasome in chronic complications of diabetes and related metabolic disorders. Cells, 9(8), 1812. doi: https://doi.org/10.3390/cells9081812
Mobasheri, L., Ahadi, M., Namdar, A. B., Alavi, M. S., Bemidinezhad, A., Farahi, S. M. M., . . . Ghorbani, A. (2023). Pathophysiology of diabetic hepatopathy and molecular mechanisms underlying the hepatoprotective effects of phytochemicals. Biomedicine & Pharmacotherapy, 167, 115502. doi: https://doi.org/10.1016/j.biopha.2023.115502
Qadri, S., & Yki-Järvinen, H. (2024). Surveillance of the liver in type 2 diabetes: important but unfeasible? diabetologia, 1-13. doi: https://doi.org/10.1007/s00125-024-06087-7
Smith, A. (2024). Impact of high-intensity interval training on cardiac health in middle-aged adults. Revista multidisciplinar de las Ciencias del Deporte, 24(96).
Solano, M. P., & Goldberg, R. B. (2006). Lipid management in type 2 diabetes. Clinical diabetes, 24(1), 27-33.
Srinivasan, K., Viswanad, B., Asrat, L., Kaul, C., & Ramarao, P. (2005). Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacological research, 52(4), 313-320. doi: https://doi.org/10.1016/j.phrs.2005.05.004
Stefan, N., & Cusi, K. (2022). A global view of the interplay between non-alcoholic fatty liver disease and diabetes. The lancet Diabetes & endocrinology, 10(4), 284-296.
Zhang, L., Ai, C., Bai, M., Niu, J., & Zhang, Z. (2022). NLRP3 inflammasome/pyroptosis: a key driving force in diabetic cardiomyopathy. International journal of molecular sciences, 23(18), 10632. doi: https://doi.org/10.3390/ijms231810632
Volume 4, Issue 3
Summer 2024
Pages 177-183

  • Receive Date 31 July 2024
  • Revise Date 11 September 2024
  • Accept Date 13 September 2024