Document Type : Original Article
Authors
Abstract
Background and Aim: Apelin that is secreted by adipose tissue plays an important role in the inflammation process and it seems could be considered as an anti-inflammatory cytokines. The aim of this study was to determine the effect of 8 weeks of endurance training and L-NAME on Apelin in adipose tissue, glucose and insulin in elderly male’s rats. Materials and Methods: For this purpose, 24 vistar elderly rats with average 22 months old purchased from Razi Institute and transferred to Research Center, they randomly divided into four groups as: control, training, L-NAME, training and L-NAME. Training protocol performed for 8 weeks and 5 days a week with 75-80 VO2max. Inhibitor-training Group with 8-week training period, were given the solution to the drinking water 75/0 mg / ml (100 mg kg mice per day) L-NAME. Inhibitors Group during the period received only supplement. All rats were killed 72 hours after the final training session and after 24 hours of fasting adipose tissue samples were collected and kept in -80 Celsius degree. Also, Data was analyzed with One way ANOVA and Tucky in p<0.05. Results: The results showed that the eight weeks of endurance exercise significantly increased the level of apelin in adipose tissue of older male rats (p=0.000). However, no changes was observed in the levels of glucose (p=0.157) and insulin (p=0.832) after endurance training in groups.
Conclusion: It seems that endurance training can increase the levels of apelin in adipose tissue independently of insulin and glucose. So probably endurance training could have a role in control inflammatory condition in elderly subjects.
Keywords
Aminilari, Z., Daryanoosh, F., Kooshki Jahromi, M., & Mohamadi, M. (2014). The effect of 12 weeks aerobic exercise on the apelin, omentin and glucose in obese older women with diabetes type 2. Arak Medical University Journal, 17(85), 1-10. [Persian]
Ashley, E., Chun, H. J., & Quertermous, T. (2006). Opposing cardiovascular roles for the angiotensin and apelin signaling pathways. Journal of Molecular and Cellular Cardiology, 41(5), 778–81.
Balon, T. W., & Nadler, J. L. (1997). Evidence that nitric oxide increases glucose transport in skeletal muscle. Journal of Applied Physiology, 82(1), 359–363.
Baron, A. D., Zhu, J. S., Marshall, S., Irsula, O., Brechtel, G., & Keech, C. (1995). Insulin resistance after hypertension induced by the nitric oxide synthesis inhibitor L-NMMA in rats. Endocrinology and Metabolism, 269(4), 709–715.
Besse-Patin, A., Montastier, E., Vinel, C., Castan-Laurell, I., Louche, K., Dray, C., Daviaud, D., Mir, L., Marques, M. A., Thalamas, C., Valet, P., Langin, D., Moro, C., & Viguerie, N. (2014). Effect of endurance training on skeletal muscle myokine expression in obese men: identification of apelin as a novel myokine. International Journal of Obesity, 38(5), 707-13.
Boucher, J., Masri, B., Daviaud, D., Gesta, S., Guigné, C., Mazzucotelli, A., Castan-Laurell, I., Tack, I., Knibiehler, B., Carpéné, C., Audigier, Y., Saulnier-Blache, J. S., & Valet, P. (2005). Apelin, a newly identified adipocyte up- regulated by insulin and obesity. Endocrinology, 146(4), 1764-71.
Carpéné, C., Dray, C., Attané, C., Valet, P., Portillo, M. P., Churruca, I., Milagro, F. I., & Castan-Laurel, I. (2007). Expanding role for the apelin/APJ system in physiopathology. Journal of Physiology and Biochemistry, 63(4), 358-373.
Castan-Laurell, I., Vítkova, M., Daviaud, D., Dray, C., Kováciková, M., Kovacova, Z., Hejnova, J., Stich, V., & Valet, P. (2008). Effect of hypocaloric diet-induced weight loss in obese women on plasma apelin and adipose tissue expression of apelin and APJ. European Journal of Endocrinology, 158(6), 905-910.
Cavallo., M. G., Sentinelli, F., Barchetta, I., Costantino, C., Incani, M., Perra, L., Capoccia, D., Romeo, S., Cossu, E., Leonetti, F., Agati, L., & Baroni, M. G. (2012). Altered glucose homeostasis is associated with increased serum apelin levels in type 2 diabetes mellitus. PloS One, 7(12), 512-36.
Dray, C., Debard, C., Jager, J., Disse, E., Daviaud, D., Martin, P., Attané, C., Wanecq, E., Guigné, C., Bost, F., Tanti, J. F., Laville, M., Vidal, H., Valet, P., & Castan-Laurel, I. (2010). Apelin and APJ regulation in adipose tissue and skeletal muscle of type 2 diabetic mice and humans. American Journal of Physiology-Endocrinology and Metabolism, 298(6), 1161-1169.
Dray, C., Knauf, C., Daviaud, D., Waget, A., Boucher, J., Buléon, M., Cani, P. D., Attané, C., Guigné, C., Carpéné, C., Burcelin, R., Castan-Laurell, I., & Valet, P. (2008). Apelin stimulates glucose utilization in normal and obese insulin-resistant mice. Cell Metabolism, 8(5), 437– 445.
Duparc, T., Colom, A., Cani, PD., Massaly, N., Rastrelli, S., Drougard, A., Le Gonidec, S., Moulédous, L., Frances, B., Leclercq, I., Llorens-Cortes, C., Pospisilik, J. A., Delzenne, N. M., Valet, P., Castan-Laurell, I., & Knauf, C. (2011). Central apelin controls glucose homeostasis via a nitric oxide-dependent pathway in mice. Antioxidants & Redox Signaling, 15(6), 1477-96.
Erdem, G., Dogru, T., Tasci, I., Sonmez, A., & Tapan, S. (2008). Low plasma apelin levels in newly diagnosed type 2 diabetes mellitus. Experimental and Clinical Endocrinology & Diabetes, 116(5)289 –292.
Frier, B. C., Williams, D. B., & Wright, D. C. (2009). The effects of apelin treatment on skeletal muscle mitochondrial content. American Journal of Physiology-Regulatory, 297(6), 1761-1768.
Fujie, S. h., Koji, S., Miyamoto, M. E., Hasegawa, N., Fujita, S., Sanada, K., Hamaoka, T., & Iemitsu, M. (2014). Reduction of arterial Stiffness by Exercise Training Is Associated with Increasing Plasma Apelin Level in Middle-Aged and Older Adults. PLoS One, 9(4), 935- 45.
Hawley, J. A., & Lessard, S. J. (2008). Exercise training-induced improvements in insulin action. Acta Physiologica, 192(1), 127-135.
Heinonen, M., Purhonen, A. K., Miettinen, P., Pääkkönen, M., Pirinen, E., Alhava, E., Akerman, K., & Herzig, K. H. (2005). Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding. Regulatory peptides, 130(1), 7-13.
Hida, K., Wada, J., Eguchi, J., Zhang, H., Baba, M., Seida, A., Hashimoto, I., Okada, T., Yasuhara, A., Nakatsuka, A., Shikata, K., Hourai, S., Futami, J., Watanabe, E., Matsuki, Y., Hiramatsu, R., Akagi, S., Makino, H., & Kanwar, Y. S. (2005). Visceral adipose tissue-derived serine protease inhibitor: a unique insulin sensitizing adipocytokine in obesity. Proceedings of the National Academy of Sciences of the United States of America, 102(30), 10610-15.
Higaki, Y., Hirshman, M. F., Fujii, N., & Goodyear, L. J. (2001). Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle. Diabetes, 50(6), 241–247.
Higuchi, K., Masaki, T., Gotoh, K., Chiba, S., Katsuragi, I., Tanaka, K., Kakuma, T., & Yoshimatsu, H. (2007). Apelin, an APJ receptor ligand, regulates body adiposity and favors the messenger ribonucleic acid expression of uncoupling proteins in mice. Endocrinology, 148(6), 2690-2697.
Ishida, J., Hashimoto, T., Hashimoto, Y., Nishiwaki, S., Iguchi, T., Harada, S., Sugaya, T., Matsuzaki, H., Yamamoto, R., Shiota, N., Okunishi, H., Kihara, M., Umemura, S., Sugiyama, F., Yagami, K., Kasuya, Y., Mochizuki, N., & Fukamizu, A. (2004). Regulatory Roles for APJ, A Seven transmembrane Receptor Related to Angiotensin-type 1 Receptor in Blood Pressure in Vivo. The Journal of Biolgical Chemistry, 279(25), 26274-79. Kadoglou, N. P., Vrabas, I. S., Kapelouzou, A., Lampropoulos, S., Sailer, N., Kostakis, A., Liapis, C. D., & Angelopoulou, N. (2012). The impact of aerobic exercise training on novel adipokines, apelin and ghrelin, in patients with type 2 diabetes. International Medical Journal of Experimental and Clinical, 18(5), 290-295.
Ma, W. Y., Yu, T. Y., Wei, J. N., Chi, S. H., Hung, C. S., Lin, M. S., Liao, Y. J., Pei, D., Su, C. C., Lu, K. C., Liu, P. H., Lin, C. H., Chuang, L. M., Kao, H. L., Lin, J. W., Chuang, Y. J., & Li, H. Y. (2014). Plasma apelin: A novel biomarker for predicting diabetes. Clinica Chimica Acta, 435(5), 18-23.
Mlinar, B., Marc, J., Janez, A., & Pfeifer, M. (2007). Molecular mechanisms of insulin resistance and associated diseases. Clinica Chimica Acta, 375(1), 20-35.
Mohebbi, H., Rhmaninia, F., Hedayati Emami, M. H., & Saidi Ziabari, T. (2014). Effects of 8-week moderate-intensity aerobic training on levels of plasma apelin and insulin resistance in women with type 2 diabetes. Physiology of Sport Journal, 5(20), 115-128. [Persian]
Naito, H., Powers, S. K., Demirel, H. A., & Aoki, J. (2001). Exercise training increases heat shock protein in skeletal muscles of old rats. Medicine and Science in Sports and Exercise, 33(5), 729- 34.
Rosen, E. D., & Spiegelman, B. M. (2006). Adipocytes as regulators of energy balance and glucose homeostasis. Nature, 444 (7121), 847-853.
Saeidi Ziabari, T., Mohebbi, H., Rahmani nia, F., & Hedayati, M.H. (2014). Effects of 8-week moderate-intensity aerobic training on levels of plasma apelin and insulin resistance in women with type 2 diabetes. Journal of Sport Physiology, 5(20), 115-128. [Persian]
Sheu, W. H., Chang, T. M., Lee W.J, Ou, H. C., Wu, C. M., Tseng, L. N., Lang, H. F, Wu, C. S., Wan, C. J., & Lee, I. T. (2008). Effect of weight loss on proinflammatory state of mononuclear cells in obese women. Obesity, 16(5), 1033-8.
Sorhede, W. M., Magnusson, C., & Ahrén, B. (2005). The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice. Regulatory Peptides, 131(1), 12-17.
Soriguer, F., Garrido-Sanchez, L., Garcia-Serrano, S., Garcia- Almeida, J. M., Tinahones, F. J., & Garcia-Fuentes, E. (2009). Apelin levels are increased in morbidly obese subjects with type 2 diabetes mellitus. Obesity Surgery, 19(11), 1574-1580.
Valle, A., Hoggard, N., Adams, A. C., Roca, P., & Speakman, J. R. (2008). Chronic Central Administration of Apelin-13 Over 10 Days Increases Food Intake, Body Weight, Locomotor Activity and Body Temperature in C57BL/6 Mice. Journal of Neuro endocrinology, 20(1), 79-84.
Varady, K. A., Tussing, L., Bhutani, S., & Braunschweig, C. L. (2009). Degree of weight loss required to improve adipokine concentrations and decrease fat cell size in severely obese women. Metabolism, 58(8), 1096-101. Xu, S., Tsao, P. S., & Yue, P. (2011). Apelin and insulin resistance: another arrow for the quiver? Journal of Diabetes, 3(3), 225-231.
Zhang, J., Ren, C. X., Qi, Y. F., Lou, L. X., Chen, L., Zhang, L. K., Wang, X., & Tang, C. (2006). Exercise training promotes expression of apelin and APJ of cardiovascular tissues in spontaneously hypertensive rats. Life Sciences, 79(12), 1153-9.
Ashley, E., Chun, H. J., & Quertermous, T. (2006). Opposing cardiovascular roles for the angiotensin and apelin signaling pathways. Journal of Molecular and Cellular Cardiology, 41(5), 778–81.
Balon, T. W., & Nadler, J. L. (1997). Evidence that nitric oxide increases glucose transport in skeletal muscle. Journal of Applied Physiology, 82(1), 359–363.
Baron, A. D., Zhu, J. S., Marshall, S., Irsula, O., Brechtel, G., & Keech, C. (1995). Insulin resistance after hypertension induced by the nitric oxide synthesis inhibitor L-NMMA in rats. Endocrinology and Metabolism, 269(4), 709–715.
Besse-Patin, A., Montastier, E., Vinel, C., Castan-Laurell, I., Louche, K., Dray, C., Daviaud, D., Mir, L., Marques, M. A., Thalamas, C., Valet, P., Langin, D., Moro, C., & Viguerie, N. (2014). Effect of endurance training on skeletal muscle myokine expression in obese men: identification of apelin as a novel myokine. International Journal of Obesity, 38(5), 707-13.
Boucher, J., Masri, B., Daviaud, D., Gesta, S., Guigné, C., Mazzucotelli, A., Castan-Laurell, I., Tack, I., Knibiehler, B., Carpéné, C., Audigier, Y., Saulnier-Blache, J. S., & Valet, P. (2005). Apelin, a newly identified adipocyte up- regulated by insulin and obesity. Endocrinology, 146(4), 1764-71.
Carpéné, C., Dray, C., Attané, C., Valet, P., Portillo, M. P., Churruca, I., Milagro, F. I., & Castan-Laurel, I. (2007). Expanding role for the apelin/APJ system in physiopathology. Journal of Physiology and Biochemistry, 63(4), 358-373.
Castan-Laurell, I., Vítkova, M., Daviaud, D., Dray, C., Kováciková, M., Kovacova, Z., Hejnova, J., Stich, V., & Valet, P. (2008). Effect of hypocaloric diet-induced weight loss in obese women on plasma apelin and adipose tissue expression of apelin and APJ. European Journal of Endocrinology, 158(6), 905-910.
Cavallo., M. G., Sentinelli, F., Barchetta, I., Costantino, C., Incani, M., Perra, L., Capoccia, D., Romeo, S., Cossu, E., Leonetti, F., Agati, L., & Baroni, M. G. (2012). Altered glucose homeostasis is associated with increased serum apelin levels in type 2 diabetes mellitus. PloS One, 7(12), 512-36.
Dray, C., Debard, C., Jager, J., Disse, E., Daviaud, D., Martin, P., Attané, C., Wanecq, E., Guigné, C., Bost, F., Tanti, J. F., Laville, M., Vidal, H., Valet, P., & Castan-Laurel, I. (2010). Apelin and APJ regulation in adipose tissue and skeletal muscle of type 2 diabetic mice and humans. American Journal of Physiology-Endocrinology and Metabolism, 298(6), 1161-1169.
Dray, C., Knauf, C., Daviaud, D., Waget, A., Boucher, J., Buléon, M., Cani, P. D., Attané, C., Guigné, C., Carpéné, C., Burcelin, R., Castan-Laurell, I., & Valet, P. (2008). Apelin stimulates glucose utilization in normal and obese insulin-resistant mice. Cell Metabolism, 8(5), 437– 445.
Duparc, T., Colom, A., Cani, PD., Massaly, N., Rastrelli, S., Drougard, A., Le Gonidec, S., Moulédous, L., Frances, B., Leclercq, I., Llorens-Cortes, C., Pospisilik, J. A., Delzenne, N. M., Valet, P., Castan-Laurell, I., & Knauf, C. (2011). Central apelin controls glucose homeostasis via a nitric oxide-dependent pathway in mice. Antioxidants & Redox Signaling, 15(6), 1477-96.
Erdem, G., Dogru, T., Tasci, I., Sonmez, A., & Tapan, S. (2008). Low plasma apelin levels in newly diagnosed type 2 diabetes mellitus. Experimental and Clinical Endocrinology & Diabetes, 116(5)289 –292.
Frier, B. C., Williams, D. B., & Wright, D. C. (2009). The effects of apelin treatment on skeletal muscle mitochondrial content. American Journal of Physiology-Regulatory, 297(6), 1761-1768.
Fujie, S. h., Koji, S., Miyamoto, M. E., Hasegawa, N., Fujita, S., Sanada, K., Hamaoka, T., & Iemitsu, M. (2014). Reduction of arterial Stiffness by Exercise Training Is Associated with Increasing Plasma Apelin Level in Middle-Aged and Older Adults. PLoS One, 9(4), 935- 45.
Hawley, J. A., & Lessard, S. J. (2008). Exercise training-induced improvements in insulin action. Acta Physiologica, 192(1), 127-135.
Heinonen, M., Purhonen, A. K., Miettinen, P., Pääkkönen, M., Pirinen, E., Alhava, E., Akerman, K., & Herzig, K. H. (2005). Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding. Regulatory peptides, 130(1), 7-13.
Hida, K., Wada, J., Eguchi, J., Zhang, H., Baba, M., Seida, A., Hashimoto, I., Okada, T., Yasuhara, A., Nakatsuka, A., Shikata, K., Hourai, S., Futami, J., Watanabe, E., Matsuki, Y., Hiramatsu, R., Akagi, S., Makino, H., & Kanwar, Y. S. (2005). Visceral adipose tissue-derived serine protease inhibitor: a unique insulin sensitizing adipocytokine in obesity. Proceedings of the National Academy of Sciences of the United States of America, 102(30), 10610-15.
Higaki, Y., Hirshman, M. F., Fujii, N., & Goodyear, L. J. (2001). Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle. Diabetes, 50(6), 241–247.
Higuchi, K., Masaki, T., Gotoh, K., Chiba, S., Katsuragi, I., Tanaka, K., Kakuma, T., & Yoshimatsu, H. (2007). Apelin, an APJ receptor ligand, regulates body adiposity and favors the messenger ribonucleic acid expression of uncoupling proteins in mice. Endocrinology, 148(6), 2690-2697.
Ishida, J., Hashimoto, T., Hashimoto, Y., Nishiwaki, S., Iguchi, T., Harada, S., Sugaya, T., Matsuzaki, H., Yamamoto, R., Shiota, N., Okunishi, H., Kihara, M., Umemura, S., Sugiyama, F., Yagami, K., Kasuya, Y., Mochizuki, N., & Fukamizu, A. (2004). Regulatory Roles for APJ, A Seven transmembrane Receptor Related to Angiotensin-type 1 Receptor in Blood Pressure in Vivo. The Journal of Biolgical Chemistry, 279(25), 26274-79. Kadoglou, N. P., Vrabas, I. S., Kapelouzou, A., Lampropoulos, S., Sailer, N., Kostakis, A., Liapis, C. D., & Angelopoulou, N. (2012). The impact of aerobic exercise training on novel adipokines, apelin and ghrelin, in patients with type 2 diabetes. International Medical Journal of Experimental and Clinical, 18(5), 290-295.
Ma, W. Y., Yu, T. Y., Wei, J. N., Chi, S. H., Hung, C. S., Lin, M. S., Liao, Y. J., Pei, D., Su, C. C., Lu, K. C., Liu, P. H., Lin, C. H., Chuang, L. M., Kao, H. L., Lin, J. W., Chuang, Y. J., & Li, H. Y. (2014). Plasma apelin: A novel biomarker for predicting diabetes. Clinica Chimica Acta, 435(5), 18-23.
Mlinar, B., Marc, J., Janez, A., & Pfeifer, M. (2007). Molecular mechanisms of insulin resistance and associated diseases. Clinica Chimica Acta, 375(1), 20-35.
Mohebbi, H., Rhmaninia, F., Hedayati Emami, M. H., & Saidi Ziabari, T. (2014). Effects of 8-week moderate-intensity aerobic training on levels of plasma apelin and insulin resistance in women with type 2 diabetes. Physiology of Sport Journal, 5(20), 115-128. [Persian]
Naito, H., Powers, S. K., Demirel, H. A., & Aoki, J. (2001). Exercise training increases heat shock protein in skeletal muscles of old rats. Medicine and Science in Sports and Exercise, 33(5), 729- 34.
Rosen, E. D., & Spiegelman, B. M. (2006). Adipocytes as regulators of energy balance and glucose homeostasis. Nature, 444 (7121), 847-853.
Saeidi Ziabari, T., Mohebbi, H., Rahmani nia, F., & Hedayati, M.H. (2014). Effects of 8-week moderate-intensity aerobic training on levels of plasma apelin and insulin resistance in women with type 2 diabetes. Journal of Sport Physiology, 5(20), 115-128. [Persian]
Sheu, W. H., Chang, T. M., Lee W.J, Ou, H. C., Wu, C. M., Tseng, L. N., Lang, H. F, Wu, C. S., Wan, C. J., & Lee, I. T. (2008). Effect of weight loss on proinflammatory state of mononuclear cells in obese women. Obesity, 16(5), 1033-8.
Sorhede, W. M., Magnusson, C., & Ahrén, B. (2005). The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice. Regulatory Peptides, 131(1), 12-17.
Soriguer, F., Garrido-Sanchez, L., Garcia-Serrano, S., Garcia- Almeida, J. M., Tinahones, F. J., & Garcia-Fuentes, E. (2009). Apelin levels are increased in morbidly obese subjects with type 2 diabetes mellitus. Obesity Surgery, 19(11), 1574-1580.
Valle, A., Hoggard, N., Adams, A. C., Roca, P., & Speakman, J. R. (2008). Chronic Central Administration of Apelin-13 Over 10 Days Increases Food Intake, Body Weight, Locomotor Activity and Body Temperature in C57BL/6 Mice. Journal of Neuro endocrinology, 20(1), 79-84.
Varady, K. A., Tussing, L., Bhutani, S., & Braunschweig, C. L. (2009). Degree of weight loss required to improve adipokine concentrations and decrease fat cell size in severely obese women. Metabolism, 58(8), 1096-101. Xu, S., Tsao, P. S., & Yue, P. (2011). Apelin and insulin resistance: another arrow for the quiver? Journal of Diabetes, 3(3), 225-231.
Zhang, J., Ren, C. X., Qi, Y. F., Lou, L. X., Chen, L., Zhang, L. K., Wang, X., & Tang, C. (2006). Exercise training promotes expression of apelin and APJ of cardiovascular tissues in spontaneously hypertensive rats. Life Sciences, 79(12), 1153-9.
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