Toll-like receptor 4 activation in skeletal muscle of diet-induced obese rats

Document Type : Original Article


1 Exercise Physiology Research Center, Life Style institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

2 Department of Biology, Yadegar-e-Imam Khomeini (RAH) Shahre Rey Branch, Islamic Azad University, Tehran, Iran.

3 PhD Student in Exercise physiology, Department of Physical Education, Faculty of Literature, Humanities and Social Sciences, Islamic Azad University Science and Research Branch, Tehran, Iran.


Toll-like receptor 4 (TLR4) is found in the membrane of skeletal muscle cells. A variety of factors can activate TLR4. It has been shown that TLR4 expression reduce after aerobic training, but more studies considering the influences of different types of training on TLR4 expression are necessary. The purpose of this study was to evaluate the influence of 8 weeks of aerobic training on muscle TLR4 Expression in rats. Twenty Male Wistar rats (200±20 g) divided into four groups: control, training, high fat diet (HFD) and HFD+exerise. High fat diet was made by adding 10% animal oil, 2% cholesterol and 0.5% colic acid to standard rodent chow. Training group performed a swimming training protocol (1 h/day, and 5 days/week for 8 weeks). Forty eight hours after the final session of training, the rats were sacrificed and their gastrocnemius muscle was removed for determination of TLR4 expression. Training significantly decreased TLR4 messenger RNA and protein expression (p<0.05). Levels of TLR4 expression in the HFD group was significantly (p<0.05) higher tahn control ones. Our result displayed that training in rats induceed a critical suppression in the TLR4 signaling in muscle. These data give noticeable progress in our knowledge of the events that link physical training to an improvement in inflammation.

What is already known on this subject?

It has been shown that TLR4 expression reduce after aerobic training, but more studies considering the influences of different types of training on TLR4 expression are necessary.


What this study adds?

Training-induced alterations in TLR4 expression might be correlated to soluble serum elements that change in response to training.


Main Subjects

Fresno, M., Alvarez, R., & Cuesta, N. (2011). Toll-like receptors, inflammation, metabolism and obesity. Archives of physiology and biochemistry, 117(3), 151-164. doi:
Gleeson, M., Bishop, N. C., Stensel, D. J., Lindley, M. R., Mastana, S. S., & Nimmo, M. A. (2011). The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nature reviews immunology, 11(9), 607-615. doi:
Jialal, I., Kaur, H., & Devaraj, S. (2014). Toll-like receptor status in obesity and metabolic syndrome: a translational perspective. The Journal of Clinical Endocrinology & Metabolism, 99(1), 39-48. doi:
Kawai, T., & Akira, S. (2011). Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity, 34(5), 637-650. doi:
Kim, J. J., & Sears, D. D. (2010). TLR4 and insulin resistance. Gastroenterology research and practice, 2010. doi:
Lira, F. S., Rosa, J. C., Pimentel, G. D., Tarini, V. A., Arida, R. M., Faloppa, F., . . . Seelaender, M. (2010). Inflammation and adipose tissue: effects of progressive load training in rats. Lipids in health and disease, 9(1), 1-10. doi:
Mignot, C. C., Pirottin, D., Farnir, F., de Moffarts, B., Molitor, C., Lekeux, P., & Art, T. (2012). Effect of strenuous exercise and ex vivo TLR3 and TLR4 stimulation on inflammatory gene expression in equine pulmonary leukocytes. Veterinary immunology and immunopathology, 147(3-4), 127-135. doi:
Nickel, T., Emslander, I., Sisic, Z., David, R., Schmaderer, C., Marx, N., . . . Weis, M. (2012). Modulation of dendritic cells and toll-like receptors by marathon running. European journal of applied physiology, 112(5), 1699-1708. doi:
Oliveira, A. G., Araujo, T. G., Carvalho, B. M., Guadagnini, D., Rocha, G. Z., Bagarolli, R. A., . . . Saad, M. J. (2013). Acute exercise induces a phenotypic switch in adipose tissue macrophage polarization in diet‐induced obese rats. Obesity, 21(12), 2545-2556. doi:
Oliveira, A. G., Carvalho, B. M., Tobar, N., Ropelle, E. R., Pauli, J. R., Bagarolli, R. A., . . . Saad, M. J. (2011). Physical exercise reduces circulating lipopolysaccharide and TLR4 activation and improves insulin signaling in tissues of DIO rats. Diabetes, 60(3), 784-796. doi:
Reyna, S. M., Tantiwong, P., Cersosimo, E., DeFronzo, R. A., Sriwijitkamol, A., & Musi, N. (2013). Short-term exercise training improves insulin sensitivity but does not inhibit inflammatory pathways in immune cells from insulin-resistant subjects. Journal of diabetes research, 2013. doi:
Rodriguez-Miguelez, P., Fernandez-Gonzalo, R., Almar, M., Mejías, Y., Rivas, A., de Paz, J. A., . . . González-Gallego, J. (2014). Role of Toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects. Age, 36(6), 1-13. doi:
Simpson, R. J., McFarlin, B. K., McSporran, C., Spielmann, G., ó Hartaigh, B., & Guy, K. (2009). Toll-like receptor expression on classic and pro-inflammatory blood monocytes after acute exercise in humans. Brain, behavior, and immunity, 23(2), 232-239. doi:
Takahashi, K., Mizuarai, S., Araki, H., Mashiko, S., Ishihara, A., Kanatani, A., . . . Kotani, H. (2003). Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. Journal of Biological Chemistry, 278(47), 46654-46660. doi:
Teerapornpuntakit, J., Dorkkam, N., Wongdee, K., Krishnamra, N., & Charoenphandhu, N. (2009). Endurance swimming stimulates transepithelial calcium transport and alters the expression of genes related to calcium absorption in the intestine of rats. American Journal of Physiology-Endocrinology and Metabolism, 296(4), E775-E786. doi:
Timmerman, K. L., Flynn, M. G., Coen, P. M., Markofski, M. M., & Pence, B. D. (2008). Exercise training‐induced lowering of inflammatory (CD14+ CD16+) monocytes: a role in the anti‐inflammatory influence of exercise? Journal of leukocyte biology, 84(5), 1271-1278. doi:
Wu, X.-D., Zeng, K., Liu, W.-L., Gao, Y.-G., Gong, C.-S., Zhang, C.-X., & Chen, Y.-Q. (2014). Effect of aerobic exercise on miRNA-TLR4 signaling in atherosclerosis. International journal of sports medicine, 35(04), 344-350. doi:
Zbinden-Foncea, H., Raymackers, J.-M., Deldicque, L., Renard, P., & Francaux, M. (2012). TLR2 and TLR4 activate p38 MAPK and JNK during endurance exercise in skeletal muscle. Medicine and science in sports and exercise, 44(8), 1463-1472. doi:
Zwagerman, N., Plumlee, C., Guthikonda, M., & Ding, Y. (2010). Toll-like receptor-4 and cytokine cascade in stroke after exercise. Neurological research, 32(2), 123-126. doi: