Research in Dance and Physical Activity

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Research in Dance and Physical Activity - Vol. 7 , No. 2

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Research in Dance and Physical Activity - Vol. 6, No. 3, pp. 51-62
ISSN: 2951-4770 (Online)
Print publication date 31 Dec 2022
Received 31 Oct 2022 Revised 13 Dec 2022 Accepted 22 Dec 2022

Effects of Different Intensities of Treadmill Exercise on Neuroinflammation and Neurotrophic Factors in High-Fat Diet-Induced Obese Mice
Su-Youn Cho1 ; Hee-Tae Roh2, *
1Yonsei University, Republic of Korea, Research Professor
2Sun Moon University, Republic of Korea, Professor

Correspondence to : *Email address:

Funding Information ▼


Obesity can impair brain health and regular exercise can effectively improve brain function. However, verification of the subclinical effects of exercise in different exercise intensities is limited. This study aimed to verify the effect of different intensities of treadmill exercise on hippocampal neuroinflammatory markers and neurotrophic factors in high-fat diet (HFD)-induced obese mice. Forty C57/black male mice received a 4-week standard diet (control, CON; n = 10) or high-fat diet (HFD; n = 30) to induce obesity. Thereafter, the HFD group was subdivided equally into the HFD + sedentary (HFDS), HFD + moderate-intensity exercise (HFDME), and HFD + high-intensity exercise (HFDHE) groups (n = 10 each). Treadmill exercises of different intensities were conducted for 8 weeks. After 8 weeks of intervention, hippocampal interferon-gamma (IFN)-γ levels were significantly lower in the CON group than in the HFDS and HFDME groups (p < 0.05), and the HFDHE group showed significantly lower IFN-γ levels than the HFDS group (p < 0.05). In addition, hippocampal nerve growth factor levels were significantly higher in the HFDME and HFDHE groups than in the CON and HFDS groups (p < 0.05). Collectively, these results suggest that obesity can induce neuroinflammation, and regular exercise can alleviate neuroinflammation and induce an increase in the expression of neurotrophic factors regardless of exercise intensity.

Keywords: obesity, exercise intensity, endurance training, neurogenesis


This work was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2019S1A5B5A07093771).

1. Agostinho, P., Cunha, R. A., & Oliveira, C. (2010). Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer's disease. Current Pharmaceutical Design, 16(25), 2766-2778.
2. An, J., Chen, B., Kang, X., Zhang, R., Guo, Y., Zhao, J., & Yang, H. (2020). Neuroprotective effects of natural compounds on LPS-induced inflammatory responses in microglia. American Journal of Translational Research, 12(6), 2353-2378.
3. Bae, J. Y. (2020). Preventive Effects of Different Aerobic Exercise Intensities on the Decline of Cognitive Function in High-Fat Diet-Induced Obese Growing Mice. Medicina, 56(7), 331.
4. Banks, W. A. (2008). The blood-brain barrier as a cause of obesity. Current Pharmaceutical Design, 14(16), 1606-1614.
5. Baranowski, B. J., Marko, D. M., Fenech, R. K., Yang, A. J. T., & MacPherson, R. E. K. (2020). Healthy brain, healthy life: a review of diet and exercise interventions to promote brain health and reduce Alzheimer's disease risk. Applied Physiology, Nutrition, and Metabolism, 45(10), 1055-1065.
6. Chaldakov, G. N., Tonchev, A. B., & Aloe, L. (2009). NGF and BDNF: from nerves to adipose tissue, from neurokines to metabokines. Rivista di Psichiatria, 44(2), 79-87.
7. El-Gharbawy, A. H., Adler-Wailes, D. C., Mirch, M. C., Theim, K. R., Ranzenhofer, L., Tanofsky-Kraff, M., & Yanovski, J. A. (2006). Serum brain-derived neurotrophic factor concentrations in lean and overweight children and adolescents. The Journal of Clinical Endocrinology and Metabolism, 91(9), 3548-3552.
8. Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry, 18(6), 499-502.
9. Ganguly, U., Kaur, U., Chakrabarti, S. S., Sharma, P., Agrawal, B. K., Saso, L., & Chakrabarti, S. (2021). Oxidative Stress, Neuroinflammation, and NADPH Oxidase: Implications in the Pathogenesis and Treatment of Alzheimer's Disease. Oxidative Medicine and Cellular Longevity, 2021, 7086512.
10. Gómez-Apo, E., Mondragón-Maya, A., Ferrari-Díaz, M., & Silva-Pereyra, J. (2021). Structural Brain Changes Associated with Overweight and Obesity. Journal of Obesity, 2021, 6613385.
11. Guillemot-Legris, O., & Muccioli, G. G. (2017). Obesity-Induced Neuroinflammation: Beyond the Hypothalamus. Trends in Neurosciences, 40(4), 237-253.
12. Hariharan, R., Odjidja, E. N., Scott, D., Shivappa, N., Hébert, J. R., Hodge, A., & de Courten, B. (2022). The dietary inflammatory index, obesity, type 2 diabetes, and cardiovascular risk factors and diseases. Obesity Reviews, 23(1), e13349.
13. Karakilic, A., Yuksel, O., Kizildag, S., Hosgorler, F., Topcugil, B., Ilgin, R., Gumus, H., Guvendi, G., Koc, B., Kandis, S., Ates, M., & Uysal, N. (2021). Regular aerobic exercise increased VEGF levels in both soleus and gastrocnemius muscles correlated with hippocampal learning and VEGF levels. Acta Neurobiologiae Experimentalis, 81(1), 1-9.
14. Kim, T. W., Choi, H. H., & Chung, Y. R. (2016). Treadmill exercise alleviates impairment of cognitive function by enhancing hippocampal neuroplasticity in the high-fat diet-induced obese mice. Journal of Exercise Rehabilitation, 12(3), 156-162.
15. Kummer, M. P., Ising, C., Kummer, C., Sarlus, H., Griep, A., Vieira-Saecker, A., Schwartz, S., Halle, A., Brückner, M., Händler, K., Schultze, J. L., Beyer, M., Latz, E., & Heneka, M. T. (2021). Microglial PD-1 stimulation by astrocytic PD-L1 suppresses neuroinflammation and Alzheimer's disease pathology. The EMBO Journal, 40(24), e108662.
16. Lang, X., Zhao, N., He, Q., Li, X., Li, X., Sun, C., & Zhang, X. (2020). Treadmill exercise mitigates neuroinflammation and increases BDNF via activation of SIRT1 signaling in a mouse model of T2DM. Brain Research Bulletin, 165, 30-39.
17. Lee, H., & Lee, H. (2018). The Roles of Dietary Polyphenols in Brain Neuromodulation. Journal of Life Science, 28(11), 1386-1395.
18. McDowell, M. L., Das, A., Smith, J. A., Varma, A. K., Ray, S. K., & Banik, N. L. (2011). Neuroprotective effects of genistein in VSC4.1 motoneurons exposed to activated microglial cytokines. Neurochemistry International, 59(2), 175-184.
19. Nakagawa, T., Ogawa, Y., Ebihara, K., Yamanaka, M., Tsuchida, A., Taiji, M., Noguchi, H., & Nakao, K. (2003). Anti-obesity and anti-diabetic effects of brain-derived neurotrophic factor in rodent models of leptin resistance. International Journal of Obesity and Related Metabolic Disorders, 27(5), 557-565.
20. Nakanishi, K., Sakakima, H., Norimatsu, K., Otsuka, S., Takada, S., Tani, A., & Kikuchi, K. (2021). Effect of low-intensity motor balance and coordination exercise on cognitive functions, hippocampal Aβ deposition, neuronal loss, neuroinflammation, and oxidative stress in a mouse model of Alzheimer's disease. Experimental Neurology, 337, 113590.
21. Pasarica, M., Sereda, O. R., Redman, L. M., Albarado, D. C., Hymel, D. T., Roan, L. E., Rood, J. C., Burk, D. H., & Smith, S. R. (2009). Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes, 58(3), 718-725.
22. Rodríguez-Hernández, H., Simental-Mendía, L. E., Rodríguez-Ramírez, G., & Reyes-Romero, M. A. (2013). Obesity and inflammation: epidemiology, risk factors, and markers of inflammation. International Journal of Endocrinology, 2013, 678159.
23. Roh, H. T., Cho, S. Y., & So, W. Y. (2017). Obesity promotes oxidative stress and exacerbates blood-brain barrier disruption after high-intensity exercise. Journal of Sport and Health Science, 6(2), 225-230.
24. Roh, H. T., & So, W. Y. (2017). The effects of aerobic exercise training on oxidant-antioxidant balance, neurotrophic factor levels, and blood-brain barrier function in obese and non-obese men. Journal of Sport and Health Science, 6(4), 447-453.
25. Sandrini, L., Di Minno, A., Amadio, P., Ieraci, A., Tremoli, E, & Barbieri, S. S. (2018). Association between Obesity and Circulating Brain-Derived Neurotrophic Factor (BDNF) Levels: Systematic Review of Literature and Meta-Analysis. International Journal of Molecular Sciences, 19(8), E2281.
26. Singhal, G., Jaehne, E. J., Corrigan, F., Toben, C., & Baune, B. T. (2014). Inflammasomes in neuroinflammation and changes in brain function: a focused review. Frontiers in Neuroscience, 8, 315.
27. Sui, S. X., & Pasco, J. A. (2020). Obesity and Brain Function: The Brain-Body Crosstalk. Medicina, 56(10), 499.
28. Van Dyken, P., & Lacoste, B. (2018). Impact of Metabolic Syndrome on Neuroinflammation and the Blood-Brain Barrier. Frontiers in Neuroscience, 12, 930.
29. Woo, J., Roh, H. T., Park, C. H., Yoon, B. K., Kim, D. Y., & Shin, K. O. (2019). Effect of resistance training at different intensities on hippocampal neurotrophic factors and peripheral CCL11 levels in obese mice. Journal of the Korean Applied Science and Technology, 36(3), 876-884.
30. Zaychik, Y., Fainstein, N., Touloumi, O., Goldberg, Y., Hamdi, L., Segal, S., Nabat, H., Zoidou, S., Grigoriadis, N., Katz, A., Ben-Hur, T., & Einstein, O. (2021). High-Intensity Exercise Training Protects the Brain Against Autoimmune Neuroinflammation: Regulation of Microglial Redox and Pro-inflammatory Functions. Frontiers in Cellular Neuroscience, 15, 640724.