Effect of exercise on body weight and insulin sensitivity following glucose loading in chronic leptin treated rats


  • Siti Nur Atika Mohd Sanif Faculty of Sports Science and Recreation, Universiti Teknologi MARA, Kampus Samarahan, Sarawak, Malaysia
  • Justin Vijay Gnanou School of Medicine, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia
  • Brinnell Annette Caszo School of Medicine, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia
  • Harbindarjeet Singh Faculty of Medicine, Universiti Teknologi MARA, Kampus Sungai Buloh, Selangor, Malaysia




leptin, glucose challenge, insulin sensitivity


Leptin affects insulin secretion and action through either a central or peripheral mechanism.  It increases glucose metabolism and energy expenditure.  Though overweight and obese individuals have been reported to have high circulating leptin levels, these effects of leptin are not evident.  Exercise, on the other hand, has been found to increase glucose uptake in these individuals.  This study examined the effect of chronic leptin treatment and exercise on body weight, glucose homeostasis and insulin sensitivity in Sprague-Dawley rats.  Eight-week old rats were treated with either intraperitoneal injection of normal saline (Control; n=8), or leptin (60 μg/kg body weight/day; Leptin; n=8), or leptin and exercise (60 μg/kg body weight/day plus running on a treadmill every other day for 30 minutes at a speed of 30 m/min with 10° inclinations; Leptin-exercise; n=8) or exercise only (running every other day for 30 minutes at a speed of 30 m/min with 10° inclinations on a treadmill; Exercise; n=8) for six weeks.  Following six weeks of treatment, glucose challenge was performed by intravenous infusion of 100 mg/ml of glucose for 5 minutes.  During the protocol, blood was drawn at 0, 5, 10, 15, 20, 25 and 30-min for blood glucose, serum glucose, and serum insulin levels determination.  Data were analyzed using One Way ANOVA with post-hoc analysis and expressed as mean ± standard error of mean (SEM).  Despite no different in body weight between the groups, leptin group had a slightly higher trend of mean body weight compared to other groups.  Glucose clearance was delayed in the leptin group.  This delay in glucose clearance might be associated with lower insulin level and action in leptin group.  More importantly, exercise reversed the leptin effects by promoting glucose clearance despite a significantly lower insulin peak, indicating increase in insulin sensitivity.  In conclusion, six weeks of daily leptin administration resulted in delayed glucose clearance, but concurrent exercise however prevented these effects of leptin by promoting glucose clearance and increasing insulin sensitivity.


Download data is not yet available.


Berti, L., & Gammeltoft, S. (1999). Leptin stimulates glucose uptake in C2C12 muscle cells by activation of ERK2. Molecular and Cellular Endocrinology, 157, 121–130.

Berti, L., Kellerer, M., Capp, E., & Haring, H. U. (1997). Leptin stimulates glucose transport and glycogen synthesis in C2C23 myotubes: evidence for a PI 3-kinase mediated effect. Diabetologia, 40(5), 606–609.

Bird, S. R., & Hawley, J. A. (2017). Update on the effects of physical activity on insulin sensitivity in humans. BJM Open Sport Exerc Med, 2(1), e000142.

Blüher, M., & Mantzoros, C. S. (2015). From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism, 64(1), 131-145.

Blüher, M., Michael, M. D., Peroni, O. D., Ueki, K., Carter, N., Kahn, B. B., & Kahn, C. R. (2002). Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Developmental Cell, 3(1), 25–38.

Bouassida, A., Chamari, K., Zaouali, M., Feki, Y., Zbidi, A., & Tabka, Z. (2010). Review on leptin and adiponectin responses and adaptations to acute and chronic exercise. Br J Sports Med, 44, 620–630.

Bouassida, A., Zalleg, D., Zaouali, M., Gharbi, N., Fekih, Y., Richalet, J. P., & Tabka, Z. (2004). Effects of supra-maximal exercise on plasma concentrations of leptin. Science & Sports, 19, 136-138.

Bradley, H., Shaw, C. S., Worthington, P. L., Shepherd, S. O., Cocks, M., & Wagenmakers, A. J. M. (2014). Quantitative immunofluorescence microscopy of subcellular GLUT4 distribution in human skeletal muscle: effects of endurance and sprint interval training. Physiological Reports, 2(7), 1–16.

Brüning, J. C., Michael, M. D., Winnay, J. N., Hayashi, T., Hörsch, D., Accili, D., Goodyear, L. J., & Kahn, C. R. (1998). A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Molecular Cell, 2(5), 559–569.

Burnett, L. C., Skowronski, A. A., Rausch, R., LeDuc, C. A., & Leibel, R. L. (2017). Determination of the half-life of circulating leptin in the mouse. International Journal of Obesity, 41(3), 355–359.

Cantley, J. (2014). The control of insulin secretion by adipokines: current evidence for adipocyte-beta cell endocrine signalling in metabolic homeostasis. Mamm Genome, 25, 442–454.

Ceddia, R. B., William Jr, W. N., & Curi, R. (1998). Leptin increases glucose transport and utilization in skeletal muscle in vitro. Gen. Pharmac, 31(5), 799–801.

Chacko E. (2016). Exercising tactically for taming postmeal glucose surges. Scientifica, 2016, 4045717.

Chen, C., Chen, H. J., Qian, L. H., Jiang, M. H., & Chen, G. Y. (2006). Effect of different blood glucose levels on the expression of cerebral GLUT3 mRNA in neonatal rats with hypoxia-ischemia. Chinese Journal of Contemporary Pediatrics, 8(5), 395–401.

Cignarelli, A., Genchi, V. A., Perrini, S., Natalicchio, A., Laviola, L., & Giorgino, F. (2019). Insulin and insulin receptors in adipose tissue development. International journal of molecular sciences, 20(3), 759.

David, B. W., John, P. H. W. (2014). Chapter 15 - Glucose metabolism and the pathophysiology of diabetes mellitus. Clinical Biochemistry: Metabolic and Clinical Aspects (Third Edition). 273-304. Churchill Livingstone

De Almeira, R. B., Pauli, L. S., de Souza, C. T., da Silva, A. S., Cintra, D. E., Marinho, R., De moura, L. P., Ropelle, E. C., & Pauli, J. R. (2014). Acute exercise decreases TRB3 protein levels in the hypothalamus of obese rats. Med Sci Sports Exerc.

De Meyts, P. (2016). The insulin receptor and its signal transducton network. In: Feingold, K. R., Anawalt, B., Boyce, A., South Dartmouth: MDText.com, Inc.; 2000-. Available from https://www.ncbi.nlm.nih.gov/books/NBK378978/

Donato Jr., J, Frazão, R. & Elias, C. F. (2010). The PI3K signaling pathway mediates the biological effects of leptin. Arquivos Brasileiros de Endocrinologia & Metabologia, 54(7), 591-602.

Douen, A. G., Ramlal, T., Rastogi, S., Bilan, P. J., Cartee, G. D., Vranic, M., Holloszy, J. O., & Klip, A. (1990). Exercise induces recruitment of the "insulin-responsive glucose transporter”. The Journal of Biological Chemistry, 265(23), 13427–13430.

Ekmen, N., Helvaci, A., Gunaldi, M., Sasani, H., & Yildirmak, S. T. (2016). Leptin as an important link between obesity and cardiovascular risk factors in men with acute myocardial infarction. Indian Heart Journal, 68(2), 132–137.

Farmawati, A., Kitajima, Y., Nedachi, T., Sato, M., Kanzaki, M., & Nagatomi, R. (2013). Characterization of contraction-induced IL-6 up-regulation using contractile C2C12 myotubes. Endocrine Journal, 60(2), 137–147.
Fernández-Formoso, G., Pérez-Sieira, S., González-Touceda, D., Dieguez, C., & Tovar, S. (2015). Leptin, 20 years of searching for glucose homeostasis. Life Sciences.

Figueira, T. R., Ribeiro, R. A., Ignacio-Sauza, L. M., Vercesi, A. E., Carneiro, E. M., & Oliveira, H. C. F. (2012). Enhanced insulin secretion and glucose tolerance in rats exhibiting low plasma free fatty acid levels and hypertriglyceridaemia due to congenital albumin deficiency. Exp Physiol, 97(4), 525-533

Friedrichsen, M., Mortensen, B., Pehmøller, C., Birk, J. B., & Wojtaszewski, J. F. P. (2012). Exercise-induced AMPK activity in skeletal muscle: Role in glucose uptake and insulin sensitivity. Molecular and Cellular Endocrinology, 1–11.

Glidden, A. R. (2010). The blunted insulin release after exercise and the relationship with gastric inhibitory polypeptide and glucagon-like peptide-1. Iowa State University.

Haron, M. N., D'Souza, U. J. A., Jaafar, H., Zakaria, R., & Singh, H. J. (2010). Exogenous leptin administration decreases sperm count and increases the fraction of abnormal sperm in adult rats. Fertility and Sterility, 93(1), 322-324.

Harris, R. B. S. (1998). Acute and chronic effects of leptin on glucose utilization in lean mice. Biochemical and Biophysical Research Communications, 245(2), 502–509.

Heath, G. W., Gavin, J. R., Hinderliter, J. M., Hagberg, J. M., Bloomfield, S. A., & Holloszy, J. O. (1983). Effects of exercise and lack of exercise on glucose tolerance and insulin sensitivity. J Appl Physiol Respir Environ Exerc Physiol, 55(2), 512–517.

Hennigar, S. R., McClung, J. P., & Pasiakos, S. M. (2017). Nutritional interventions and the IL-6 response to exercise. The FASEB Journal, 31, 3719-3728.

Houseknecht, K. L., & Portocarrero, C. P. (1998). Leptin and its receptors : regulators of whole-body energy homeostasis. Domest Anim Endocrinol, 15(6), 457–475.

Ibrahim, K. S., Omar, E., Ruth, G., Froemming, A., & Singh, H. J. (2013). Leptin increases blood pressure and markers of endothelial activation during pregnancy in rats. BioMed Research International, 2013.

Ishii, T., Yamakita, T., Yamagami, K., Yamamoto, T., Miyamoto, M., Kawasaki, K., Hosoi, M., Yoshioka, K., Sato, T., Tanaka, S., & Fujii, S. (2001). Effect of exercise training on serum leptin levels in type 2 diabetic patients. Metabolism, 50(10), 1136–1140.

Jensen, T. E., & Richter, E. A. (2012). Regulation of glucose and glycogen metabolism during and after exercise. J Physiol, 590.5(March), 1069–1076.

Jensen, T. E., Sylow, L., Rose, A. J., Madsen, A. B., Angin, Y., Maarbjerg, S. J., & Richter, E. A. (2014). Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca2+ release. Molecular Metabolism, 3(7), 742–753.

Jimenez-Pavon, D., Ortega, F. B., Artero, E. G., Labayen, I., Vicente-Rodriguez, G., Huybrechts, I., Moreno, L. A., Sjostrom, M., Castillo, M. J., Gonzalez-Gross, M., & Ruiz, J. R. (2012). Physical activity, fitness, and serum leptin concentrations in adolescents. The Journal of Pediatrics, 160(4), 598-603.

Joseph, J. W., Koshkin, V., Saleh, M. C., Sivitz, W. I., Zhang, C.-Y., Lowell, B. B., … Wheeler, M. B. (2004). Free Fatty Acid-induced β-Cell Defects Are Dependent on Uncoupling Protein 2 Expression. Journal of Biological Chemistry, 279(49), 51049–51056.

Kang, S., Kim, K. B., & Shin, K. O. (2013). Exercise training improve leptin sensitivity in peripheral tissueof obese rats. Biochemical and Biophysical Research Communications, 435(3), 454-459.

Katherine, A. T., Alexandra, J. M. & Jessica, H. B. (2019). Chapter 12 - Influence of hormone on the development of eating disorder. Eating disorders and obesity in children and adolescents. Elsevier. 73-77. ISBN 9780323548526.

Kumar, M. V., Shimokawa, T., Nagy, T. R., & Lane, M. D. (2002). Differential effects of a centrally acting fatty acid synthase inhibitor in lean and obese mice. Proceedings of the National Academy of Sciences of the United States of America, 99(4), 1921–1925.

Lalanza, J. F., Sanchez-Roige, S., Cigarroa, I., Gagliano, H., Fuentes, S., Armario, A., Capdevila, L., & Escorihuela, R. M. (2015). Long-term moderate treadmill exercise promotes stress-coping strategies in male and female rats. Scientific Reports, 5:16166.

Lee, C., Lee, C., Tsai, S., Huang, C., Wu, M., Tai, S.-Y., Lin, F.-F., Chao, N.-C., & Chang, C.-J. (2009). Association between serum leptin and adiponectin levels with risk of insulin resistance and impaired glucose tolerance in non-diabetic women. The Kaohsiung Journal of Medical Sciences, 25(3), 116–125.

Leto, D., & Saltiel, A. R. (2012). Regulation of glucose transport by insulin: traffic control of GLUT4. Nature Reviews Molecular Cell Biology, 13(6), 383-396.

Liu, J., Wu, X., Franklin, J. L., Messina, J. L., Hill, H. S., Moellering, D. R., Walton, R. G., Martin, M., & Garvey, W. T. (2010). Mammalian Tribbles homolog 3 impairs insulin action in skeletal muscle: role in glucose-induced insulin resistance. Am J Physiol Endocrinol Metab, 298, E565–E576.

Lund, S., Holmant, G. D., Schmitz, O., & Pedersen, O. (1995). Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. Proceedings of the National Academy of Sciences of the United States of America, 92(13), 5817–5821.

Marinho, R., Mekary, R. A., Muñoz, V. R., Gomes, R. J., Pauli, J. R., & de Moura, L. P. (2015). Regulation of hepatic TRB3/Akt interaction induced by physical exercise and its effect on the hepatic glucose production in an insulin resistance state. Diabetology & Metabolic Syndrome, 7, 67.

Melmer, A., Kempf, P., Laimer, M. (2018). The role of physical exercise in obesity and diabetes. Praxis, 107, 971-976.

Messina, G., Palmieri, F., Monda, V., Messina, A., Dalia, C., Viggiano, A., Tafuri, D., Moscatelli, F., Valenzano, A., Cibelli, G., Chieffi, S., & Monda, M. (2015). Exercise causes muscle GLUT4 translocation in an insulin-independent manner. Biol Med (Aligarh), 1:006.

Mizgier, M. L., Casas, M., Contreras-Ferrat, A., Llanos, P., & Galgani, J. E. (2014). Potential role of skeletal muscle glucose metabolism on the regulation of insulin secretion. Obesity Reviews, 15(7), 587–597.

Nuri, R., Moghaddasi, M., Darvishi, H., Izadpanah, A. (2016). Effect of aerobic exercise on leptin and ghrelin in patients with colorectal cancer. Journal of Cancer Research and Therapeutics, 12(1), 169-174.

Ostrowski, K., Rohde, T., Asp, S., Schjerling, P., & Pedersen, B. K. (1999). Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. Journal of Physiology, 515(1), 287–291.

Park, H.-K., & Ahima, R. S. (2014). Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism, 1–11.

Paz-Filho, G., Mastronardi, C. A., & Licinio, J. (2014). Leptin treatment: Facts and expectations. Metabolism.

Röder, P. V., Wu, B., Liu, Y., & Han, W. (2016). Pancreatic regulation of glucose homeostasis. Experimental & Molecular Medicine, 48(3), e219.

Röhling, M., Herder, C., Stemper, T., & Müssig, K. (2016). Influence of acute and chronic exercise on glucose uptake. J Diabetes Res, 1-33.

Sáinz, N., Barrenetxe, J., Moreno-Aliaga, M. J., & Martínez, J. A. (2015). Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism, 64(1), 35-46.

Sari, R, Balci, M. K., & Apaydin, C. (2010). The relationship between plasma leptin levels and chronic compilation in patients with type 2 diabetes mellitus. Metabolic Syndrome and Related Disorder, 8(6), 499-503.

Sasaki, H., Ohtsu, T., Ikeda, Y., Tsubosaka, M., & Shibata, S. (2014). Combination of meal and exercise timing with a high-fat diet influences energy expenditure and obesity in mice. Chronobiology International, 1–17.

Singh, H. J., & Garland, H. O. (1989). A comparison of the effects of oral and intravenous glucose administration on renal calcium excretion in the rat. Quarterly Journal of Experimental Physiology, 74, 531–540.

Sjøberg, K. A., Frøsig, C., Kjøbsted, R., Sylow, L., Kleinert, M., Betik, A. C., Shaw, C. S., Kiens, B., Wojtaszewski, J. F. P., Rattigan, S., Richter, E. A. and McConell, G. K. (2017). Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling. Diabetes, 66(6), 1501-1510.

Way, K. L., Hackett, D. A., Baker, M. K., & Johnson, N. A. (2016). The effect of regular exercise on insulin sensitivity in type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes & Metabolism Journal, 40(4), 253–271.

Wojtaszewski, J. F. P., Higaki, Y., Hirshman, M. F., Michael, M. D., Dufresne, S. D., Kahn, C. R., & Goodyear, L. J. (1999). Exercise modulates postreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice. The Journal of Clinical Investigation, 104(9), 1257–1264.

Zeng, J., Patterson, B. W., Klein, S., Martin, D. R., Dagogo-Jack, S., Kohrt, W. M., Miller, S. B., & Landt, M. (1997). Whole body leptin kinetics and renal metabolism in vivo. The American Journal of Physiology, 273(6 Pt 1), E1102–E1106.




How to Cite

Mohd Sanif, S. N. A., Gnanou, J. V., Caszo, B. A., & Singh, H. (2019). Effect of exercise on body weight and insulin sensitivity following glucose loading in chronic leptin treated rats. Jurnal Sains Sukan & Pendidikan Jasmani, 8(1), 1–12. https://doi.org/10.37134/jsspj.vol8.1.1.2019