The Effect of Combined Training and Caffeine Supplementation on Toll-like Receptor 2 (TLR2), TLR4, and Dectin-1 in Obese Men
Subject Areas : Microbiology
SH.
Ghaderi Goodarzi
1
(PhD Student of the Department of Exercise Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.)
A.
Abbassi Daloii
2
(Associate Professor of the Department of Exercise Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.)
A.
Abdi
3
(Associate Professor of the Department of Exercise Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.)
A.
Saeidi
4
(Assistant Professor of the Department of Exercise Physiology, Damghan Branch, Islamic Azad University, Damghan, Iran.)
Keywords: Caffeine Chronic Inflammation, Combined Training, Obesity,
Abstract :
Introduction: Overweight and obesity are associated with increased inflammatory conditions and metabolic disorders. A therapeutic agent that can suppress metabolic and immune disorders may effectively ameliorate parallel abnormalities in obesity. The aim of this study was to evaluate the effect of combined training and caffeine supplementation on Toll-like receptor 2 (TLR2), TLR4, and dectin-1 in obese men. Materials and Methods: In a semi-experimental trial, 44 obese men were purposefully and accessibly selected and randomly divided into four groups: 1) control, 2) combined training, 3) caffeine and 4) combined training -caffeine. Subjects received 6 mg of caffeine per kilogram of body weight daily for 12 weeks. The combined training program include circular resistance training (3 times with 14 repetitions at 50% of one maximum repetition and 30 seconds rest between each station) and aerobic exercise (70% maximum heart rate for 30 minutes) was performed 3 sessions per week for 12 weeks. The combined training program was performed for 12 weeks and 3 sessions per week. Data were analyzed with covariance analysis and Tukey post hoc test at the p<0.05.Results: The results showed that 12 weeks of combined training, caffeine and combined training - caffeine significantly reduced serum levels of TLR2, TLR4 and Dectin-1 (P=0.001). The reduce of serum levels of TLR2, TLR4 and Dectin-1 were significant in the combined training compared to caffeine group (P=0.001). the effect of interactive combined training with caffeine was more than supplementation and training alone.Conclusion: According to the findings, it is suggested that combined training intervention with caffeine consumption be used in order to reduce its inflammatory effects associated with obesity.
Castoldi, A., Andrade-Oliveira, V., Aguiar, C. F., Amano, M. T., Lee, J., Miyagi, M. T., Latância, M. T., Braga, T. T., da Silva, M. B., Ignácio, A., Carola Correia Lima, J. D., Loures, F. V., Albuquerque, J., Macêdo, M. B., Almeida, R. R., Gaiarsa, J. W., Luévano-Martínez, L. A., Belchior, T., Hiyane, M. I., Brown, G. D. & Câmara, N. (2017). Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88. Cell Reports, 19(11), 2272–2288.
Cortez-Espinosa, N., García-Hernández, M. H., Reynaga-Hernández, E., Cortés-García, J. D., Corral-Fernández, N. E., Rodríguez-Rivera, J. G., Bravo-Ramírez, A., González-Amaro, R. & Portales-Pérez, D. P. (2012). Abnormal expression and function of Dectin-1 receptor in type 2 diabetes mellitus patients with poor glycemic control (HbA1c>8%). Metabolism: Clinical and Experimental, 61(11), 1538–1546.
Cristofaro, P. & Opal, S. M. (2006). Role of Toll-like receptors in infection and immunity: clinical implications. Drugs, 66(1), 15–29.
de Alcântara Almeida, I., Mancebo Dorvigny, B., Souza Tavares, L., Nunes Santana, L. & Vitor Lima-Filho, J. (2021). Anti-inflammatory activity of caffeine (1,3,7-trimethylxanthine) after experimental challenge with virulent Listeria monocytogenes in Swiss mice. International Immunopharmacology, 100, 108090.
del Fresno, C., Soulat, D., Roth, S., Blazek, K., Udalova, I., Sancho, D., Ruland, J. & Ardavín, C. (2013). Interferon-β production via Dectin-1-Syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans. Immunity, 38(6), 1176–1186.
Ebrahim, K., bassami, M., kolahdozi, S. & Karimnia Saheb, V. (2012). The Effects of Circuit Resistance Exercise on Fat and Carbohydrate Metabolism During Endurance Exercise in Overweight Men. Iranian Journal of Endocrinology and Metabolism, 14(3), 257-66 [In Persian].
Favere, K., Bosman, M., Delputte, P. L., Favoreel, H. W., Van Craenenbroeck, E. M., De Sutter, J., Witvrouwen, I., De Meyer, G., Heidbuchel, H. & Guns, P. (2021). A systematic literature review on the effects of exercise on human Toll-like receptor expression. Exercise Immunology Review, 27, 84–124.
Feng, Y. & Chao, W. (2011). Toll-like receptors and myocardial inflammation. International Journal of Inflammation, 170352.
Fernandez-Gonzalo, R., De Paz, J. A., Rodriguez-Miguelez, P., Cuevas, M. J. & González-Gallego, J. (2014). TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women. Mediators of Inflammation, 479395.
Fontana, L., Klein, S. & Holloszy, J. O. (2010). Effects of long-term calorie restriction and endurance exercise on glucose tolerance,
insulin action, and adipokine production. Age (Dordrecht, Netherlands), 32(1), 97–108.
Francaux, M. (2009). Toll-like receptor signalling induced by endurance exercise. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 34(3):454–458.
Gantner, B. N., Simmons, R. M., Canavera, S. J., Akira, S. & Underhill, D. M. (2003). Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. The Journal of Experimental Medicine, 197(9), 1107–1117.
Jessen, A., Buemann, B., Toubro, S., Skovgaard, I. M. & Astrup, A. (2005). The appetite-suppressant effect of nicotine is enhanced by caffeine. Diabetes, Obesity & Metabolism, 7(4), 327–333.
Kalia, N., Singh, J. & Kaur, M. (2021). The role of dectin-1 in health and disease. Immunobiology, 226 (2), 152071.
Kawai, T. & Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunology, 11(5), 373–384.
Kobayashi-Hattori, K., Mogi, A., Matsumoto, Y. & Takita, T. (2005). Effect of caffeine on the body fat and lipid metabolism of rats fed on a high-fat diet. Bioscience, Biotechnology, and Biochemistry, 69(11), 2219–2223.
Kolb, H., Martin, S. & Kempf, K. (2021). Coffee and Lower Risk of Type 2 Diabetes: Arguments for a Causal Relationship. Nutrients, 13(4), 1144.
Krausgruber, T., Blazek, K., Smallie, T., Alzabin, S., Lockstone, H., Sahgal, N., Hussell, T., Feldmann, M. & Udalova, I. A. (2011). IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nature Immunology, 12(3), 231–238.
Lee W. J. (2011). IGF-I Exerts an Anti-inflammatory Effect on Skeletal Muscle Cells through Down-regulation of TLR4 Signaling. Immune Network, 11(4), 223–226.
Liu, C. W., Tsai, H. C., Huang, C. C., Tsai, C. Y., Su, Y. B., Lin, M. W., Lee, K. C., Hsieh, Y. C., Li, T. H., Huang, S. F., Yang, Y. Y., Hou, M. C., Lin, H. C., Lee, F. Y. & Lee, S. D. (2018). Effects and mechanisms of caffeine to improve immunological and metabolic abnormalities in diet-induced obese rats. American journal of physiology. Endocrinology and Metabolism, 314(5), E433–E447.
McFarlin, B. K., Flynn, M. G., Campbell, W. W., Craig, B. A., Robinson, J. P., Stewart, L. K., Timmerman, K. L. & Coen, P. M. (2006). Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4. The journals of gerontology. Series A, Biological Sciences and Medical Sciences, 61(4), 388–393.
McFarlin, B. K., Flynn, M. G., Campbell, W. W., Stewart, L. K. & Timmerman, K. L. (2004). TLR4 is lower in resistance-trained older women and related to inflammatory cytokines. Medicine and Science in Sports and Exercise, 36(11), 1876–1883.
Medzhitov, R. (2001). Toll-like receptors and innate immunity. Nature Reviews Immunology, 1(2), 135–145.
Pahl, H. L. (1999). Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene, 18(49), 6853–6866.
Reid, D. M., Montoya, M., Taylor, P. R., Borrow, P., Gordon, S., Brown, G. D. & Wong, S. Y. (2004). Expression of the{beta}-glucan receptor, Dectin-1, on murine leukocytes insitu correlates with its function in pathogen recognition andreveals potential roles in leukocyte interactions. Journal of Leukocyte Biology, 76, 86–94.
Rodas, L., Riera-Sampol, A., Aguilo, A., Martínez, S. & Tauler, P. (2020). Effects of Habitual Caffeine Intake, Physical Activity Levels, and Sedentary Behavior on the Inflammatory Status in a Healthy Population. Nutrients, 12(8), 2325.
Rodriguez-Miguelez, P., Fernandez-Gonzalo, R., Collado, P. S., Almar, M., Martinez-Florez, S., de Paz, J. A., González-Gallego, J. & Cuevas, M. J. (2015). Whole-body vibration improves the anti-inflammatory status in elderly subjects through toll-like receptor 2 and 4 signaling pathways. Mechanisms of Ageing and Development, 150, 12–19.
Rosa, J. C., Lira, F. S., Eguchi, R., Pimentel, G. D., Venâncio, D. P., Cunha, C. A., Oyama, L. M., De Mello, M. T., Seelaender, M. & do Nascimento, C. M. (2011). Exhaustive exercise increases inflammatory response via Toll like receptor-4 and NF-κBp65 pathway in rat adipose tissue. Journal of Cellular Physiology, 226(6), 1604–1607.
Ruffino, J. S., Davies, N. A., Morris, K., Ludgate, M., Zhang, L., Webb, R. & Thomas, A. W. (2016). Moderate-intensity exercise alters markers of alternative activation in circulating monocytes in females: a putative role for PPARγ. European Journal of Applied Physiology, 116(9), 1671–1682.
Schubert, M. M., Hall, S., Leveritt, M., Grant, G., Sabapathy, S. & Desbrow, B. (2014). Caffeine consumption around an exercise bout: effects on energy expenditure, energy intake, and exercise enjoyment. Journal of applied physiology (Bethesda, Md. : 1985), 117(7), 745–754
Thiagarajan, P. S., Yakubenko, V. P., Elsori, D. H., Yadav, S. P., Willard, B., Tan, C. D., Rodriguez, E. R., Febbraio, M. & Cathcart, M. K. (2013). Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1. Cardiovascular Research, 99(3), 494–504.
Wang, Z., Ni, X., Zhang, L., Sun, L., Zhu, X., Zhou, Q., Yang, Z. & Yuan, H. (2020). Toll-Like Receptor 4 and Inflammatory Micro-Environment of Pancreatic Islets in Type-2 Diabetes Mellitus: A Therapeutic Perspective. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 13, 4261–4272.
Willment, J. A., Marshall, A. S., Reid, D. M., Williams, D. L., Wong, S. Y., Gordon, S. & Brown, G. D. (2005). The human beta-glucan receptor is widely expressed and functionally equivalent to murine Dectin-1 on primary cells. European Journal of Immunology, 35(5), 1539–1547.
Wu, H. & Ballantyne, C. M. (2020). Metabolic Inflammation and Insulin Resistance in Obesity. Circulation Research, 126(11), 1549–1564.
Yamauchi, R., Kobayashi, M., Matsuda, Y., Ojika, M., Shigeoka, S., Yamamoto, Y., Tou, Y., Inoue, T., Katagiri, T., Murai, A. & Horio, F. (2010). Coffee and caffeine ameliorate hyperglycemia, fatty liver, and inflammatory adipocytokine expression in spontaneously diabetic KK-Ay mice. Journal of Agricultural and Food Chemistry, 58(9), 5597–5603.
Zanchi, N. E., Lira, F. S., de Siqueira Filho, M. A., Rosa, J. C., de Oliveira Carvalho, C. R., Seelaender, M., Santos, R. V. & Lancha, A. H. (2010). Chronic low frequency/low volume resistance training reduces pro-inflammatory cytokine protein levels and TLR4 mRNA in rat skeletal muscle. European Journal of Applied Physiology, 109(6), 1095–1102.
Zhang, S. J., Li, Y. F., Wang, G. E., Tan, R. R., Tsoi, B., Mao, G. W., Zhai, Y. J., Cao, L. F., Chen, M., Kurihara, H., Wang, Q. & He, R. R. (2015). Caffeine ameliorates high energy diet-induced hepatic steatosis: sirtuin 3 acts as a bridge in the lipid metabolism pathway. Food & Function, 6, 2578–2587.
_||_Castoldi, A., Andrade-Oliveira, V., Aguiar, C. F., Amano, M. T., Lee, J., Miyagi, M. T., Latância, M. T., Braga, T. T., da Silva, M. B., Ignácio, A., Carola Correia Lima, J. D., Loures, F. V., Albuquerque, J., Macêdo, M. B., Almeida, R. R., Gaiarsa, J. W., Luévano-Martínez, L. A., Belchior, T., Hiyane, M. I., Brown, G. D. & Câmara, N. (2017). Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88. Cell Reports, 19(11), 2272–2288.
Cortez-Espinosa, N., García-Hernández, M. H., Reynaga-Hernández, E., Cortés-García, J. D., Corral-Fernández, N. E., Rodríguez-Rivera, J. G., Bravo-Ramírez, A., González-Amaro, R. & Portales-Pérez, D. P. (2012). Abnormal expression and function of Dectin-1 receptor in type 2 diabetes mellitus patients with poor glycemic control (HbA1c>8%). Metabolism: Clinical and Experimental, 61(11), 1538–1546.
Cristofaro, P. & Opal, S. M. (2006). Role of Toll-like receptors in infection and immunity: clinical implications. Drugs, 66(1), 15–29.
de Alcântara Almeida, I., Mancebo Dorvigny, B., Souza Tavares, L., Nunes Santana, L. & Vitor Lima-Filho, J. (2021). Anti-inflammatory activity of caffeine (1,3,7-trimethylxanthine) after experimental challenge with virulent Listeria monocytogenes in Swiss mice. International Immunopharmacology, 100, 108090.
del Fresno, C., Soulat, D., Roth, S., Blazek, K., Udalova, I., Sancho, D., Ruland, J. & Ardavín, C. (2013). Interferon-β production via Dectin-1-Syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans. Immunity, 38(6), 1176–1186.
Ebrahim, K., bassami, M., kolahdozi, S. & Karimnia Saheb, V. (2012). The Effects of Circuit Resistance Exercise on Fat and Carbohydrate Metabolism During Endurance Exercise in Overweight Men. Iranian Journal of Endocrinology and Metabolism, 14(3), 257-66 [In Persian].
Favere, K., Bosman, M., Delputte, P. L., Favoreel, H. W., Van Craenenbroeck, E. M., De Sutter, J., Witvrouwen, I., De Meyer, G., Heidbuchel, H. & Guns, P. (2021). A systematic literature review on the effects of exercise on human Toll-like receptor expression. Exercise Immunology Review, 27, 84–124.
Feng, Y. & Chao, W. (2011). Toll-like receptors and myocardial inflammation. International Journal of Inflammation, 170352.
Fernandez-Gonzalo, R., De Paz, J. A., Rodriguez-Miguelez, P., Cuevas, M. J. & González-Gallego, J. (2014). TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women. Mediators of Inflammation, 479395.
Fontana, L., Klein, S. & Holloszy, J. O. (2010). Effects of long-term calorie restriction and endurance exercise on glucose tolerance,
insulin action, and adipokine production. Age (Dordrecht, Netherlands), 32(1), 97–108.
Francaux, M. (2009). Toll-like receptor signalling induced by endurance exercise. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 34(3):454–458.
Gantner, B. N., Simmons, R. M., Canavera, S. J., Akira, S. & Underhill, D. M. (2003). Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. The Journal of Experimental Medicine, 197(9), 1107–1117.
Jessen, A., Buemann, B., Toubro, S., Skovgaard, I. M. & Astrup, A. (2005). The appetite-suppressant effect of nicotine is enhanced by caffeine. Diabetes, Obesity & Metabolism, 7(4), 327–333.
Kalia, N., Singh, J. & Kaur, M. (2021). The role of dectin-1 in health and disease. Immunobiology, 226 (2), 152071.
Kawai, T. & Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunology, 11(5), 373–384.
Kobayashi-Hattori, K., Mogi, A., Matsumoto, Y. & Takita, T. (2005). Effect of caffeine on the body fat and lipid metabolism of rats fed on a high-fat diet. Bioscience, Biotechnology, and Biochemistry, 69(11), 2219–2223.
Kolb, H., Martin, S. & Kempf, K. (2021). Coffee and Lower Risk of Type 2 Diabetes: Arguments for a Causal Relationship. Nutrients, 13(4), 1144.
Krausgruber, T., Blazek, K., Smallie, T., Alzabin, S., Lockstone, H., Sahgal, N., Hussell, T., Feldmann, M. & Udalova, I. A. (2011). IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nature Immunology, 12(3), 231–238.
Lee W. J. (2011). IGF-I Exerts an Anti-inflammatory Effect on Skeletal Muscle Cells through Down-regulation of TLR4 Signaling. Immune Network, 11(4), 223–226.
Liu, C. W., Tsai, H. C., Huang, C. C., Tsai, C. Y., Su, Y. B., Lin, M. W., Lee, K. C., Hsieh, Y. C., Li, T. H., Huang, S. F., Yang, Y. Y., Hou, M. C., Lin, H. C., Lee, F. Y. & Lee, S. D. (2018). Effects and mechanisms of caffeine to improve immunological and metabolic abnormalities in diet-induced obese rats. American journal of physiology. Endocrinology and Metabolism, 314(5), E433–E447.
McFarlin, B. K., Flynn, M. G., Campbell, W. W., Craig, B. A., Robinson, J. P., Stewart, L. K., Timmerman, K. L. & Coen, P. M. (2006). Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4. The journals of gerontology. Series A, Biological Sciences and Medical Sciences, 61(4), 388–393.
McFarlin, B. K., Flynn, M. G., Campbell, W. W., Stewart, L. K. & Timmerman, K. L. (2004). TLR4 is lower in resistance-trained older women and related to inflammatory cytokines. Medicine and Science in Sports and Exercise, 36(11), 1876–1883.
Medzhitov, R. (2001). Toll-like receptors and innate immunity. Nature Reviews Immunology, 1(2), 135–145.
Pahl, H. L. (1999). Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene, 18(49), 6853–6866.
Reid, D. M., Montoya, M., Taylor, P. R., Borrow, P., Gordon, S., Brown, G. D. & Wong, S. Y. (2004). Expression of the{beta}-glucan receptor, Dectin-1, on murine leukocytes insitu correlates with its function in pathogen recognition andreveals potential roles in leukocyte interactions. Journal of Leukocyte Biology, 76, 86–94.
Rodas, L., Riera-Sampol, A., Aguilo, A., Martínez, S. & Tauler, P. (2020). Effects of Habitual Caffeine Intake, Physical Activity Levels, and Sedentary Behavior on the Inflammatory Status in a Healthy Population. Nutrients, 12(8), 2325.
Rodriguez-Miguelez, P., Fernandez-Gonzalo, R., Collado, P. S., Almar, M., Martinez-Florez, S., de Paz, J. A., González-Gallego, J. & Cuevas, M. J. (2015). Whole-body vibration improves the anti-inflammatory status in elderly subjects through toll-like receptor 2 and 4 signaling pathways. Mechanisms of Ageing and Development, 150, 12–19.
Rosa, J. C., Lira, F. S., Eguchi, R., Pimentel, G. D., Venâncio, D. P., Cunha, C. A., Oyama, L. M., De Mello, M. T., Seelaender, M. & do Nascimento, C. M. (2011). Exhaustive exercise increases inflammatory response via Toll like receptor-4 and NF-κBp65 pathway in rat adipose tissue. Journal of Cellular Physiology, 226(6), 1604–1607.
Ruffino, J. S., Davies, N. A., Morris, K., Ludgate, M., Zhang, L., Webb, R. & Thomas, A. W. (2016). Moderate-intensity exercise alters markers of alternative activation in circulating monocytes in females: a putative role for PPARγ. European Journal of Applied Physiology, 116(9), 1671–1682.
Schubert, M. M., Hall, S., Leveritt, M., Grant, G., Sabapathy, S. & Desbrow, B. (2014). Caffeine consumption around an exercise bout: effects on energy expenditure, energy intake, and exercise enjoyment. Journal of applied physiology (Bethesda, Md. : 1985), 117(7), 745–754
Thiagarajan, P. S., Yakubenko, V. P., Elsori, D. H., Yadav, S. P., Willard, B., Tan, C. D., Rodriguez, E. R., Febbraio, M. & Cathcart, M. K. (2013). Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1. Cardiovascular Research, 99(3), 494–504.
Wang, Z., Ni, X., Zhang, L., Sun, L., Zhu, X., Zhou, Q., Yang, Z. & Yuan, H. (2020). Toll-Like Receptor 4 and Inflammatory Micro-Environment of Pancreatic Islets in Type-2 Diabetes Mellitus: A Therapeutic Perspective. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 13, 4261–4272.
Willment, J. A., Marshall, A. S., Reid, D. M., Williams, D. L., Wong, S. Y., Gordon, S. & Brown, G. D. (2005). The human beta-glucan receptor is widely expressed and functionally equivalent to murine Dectin-1 on primary cells. European Journal of Immunology, 35(5), 1539–1547.
Wu, H. & Ballantyne, C. M. (2020). Metabolic Inflammation and Insulin Resistance in Obesity. Circulation Research, 126(11), 1549–1564.
Yamauchi, R., Kobayashi, M., Matsuda, Y., Ojika, M., Shigeoka, S., Yamamoto, Y., Tou, Y., Inoue, T., Katagiri, T., Murai, A. & Horio, F. (2010). Coffee and caffeine ameliorate hyperglycemia, fatty liver, and inflammatory adipocytokine expression in spontaneously diabetic KK-Ay mice. Journal of Agricultural and Food Chemistry, 58(9), 5597–5603.
Zanchi, N. E., Lira, F. S., de Siqueira Filho, M. A., Rosa, J. C., de Oliveira Carvalho, C. R., Seelaender, M., Santos, R. V. & Lancha, A. H. (2010). Chronic low frequency/low volume resistance training reduces pro-inflammatory cytokine protein levels and TLR4 mRNA in rat skeletal muscle. European Journal of Applied Physiology, 109(6), 1095–1102.
Zhang, S. J., Li, Y. F., Wang, G. E., Tan, R. R., Tsoi, B., Mao, G. W., Zhai, Y. J., Cao, L. F., Chen, M., Kurihara, H., Wang, Q. & He, R. R. (2015). Caffeine ameliorates high energy diet-induced hepatic steatosis: sirtuin 3 acts as a bridge in the lipid metabolism pathway. Food & Function, 6, 2578–2587.
