Possible crosstalk between leptin and insulin resistance in sedentary obese boys at different stages of puberty

Document Type : Original Article


1 Assistant Professor, Department of Physical Education, Faculty of Humanities, Islamic Azad University, Rasht Branch, Rasht, Iran.

2 Faculty of Physical Education and Sport Sciences, Department of Exercise Physiology, University of Guilan, Rasht, Iran

3 Exercise Physiology Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran


Puberty with interactive growth in tissues is a sensitive period in life that can be more affected by obesity. Also the increase of leptin and insulin resistant independent of obesity have been seen in puberty. The aim of our study was to investigate the role of puberty on changes in leptin, testosterone, and insulin resistance in sedentary obese boy with considering possible crosstalk between leptin and insulin resistance. 58 sedentary obese boys (14.10 + 1.37 years) participated in this study. Tanner stage scales were used to measure puberty by self-reporting. Initially anthropometric characteristics and then, fasting serum’s glucose, insulin, leptin and testosterone, were measured. With increasing mature from TS2 to TS5, the increasing of testosterone, body mass and lean body mass and the reduction of body fat percentage were significantly (p≤0.05). but the changes in leptin and HOMA-IR were not significant. However, the decreased leptin after adjusting for BMI between TS3 and TS4 were significant (p≤0.05). During puberty, rapid growth in muscle tissue were associated with decreased body fat percent, serum leptin and insulin resistance. Among the possible reasons is a 15-fold increase in serum testosterone from TS2 to TS5. These changes reflect the cross talk between muscle and adipose tissue by hormonal mediators.

What is already known on this subject?

In previous studies, the role of leptin and insulin resistance in metabolic disease was investigated.


What this study adds?

In our study, it was shown that puberty can be effective in crosstalk between leptin, insulin and insulin resistance. However, it is suggested that in future studies, the role of exercise training during puberty be measured with these indicators.


Main Subjects

Ackel-D’Elia, C., Carnier, J., Bueno Jr, C., Campos, R., Sanches, P., Clemente, A., . . . Dâmaso, A. (2014). Effects of different physical exercises on leptin concentration in obese adolescents. International journal of sports medicine, 35(2), 164-171. Doi: 10.1055/s-0033-1345128
Aguilar-Gomez, F., Bueno-Lozano, G., Leis, R., Aguilera, C., & Gil-Campos, M. (2020). Metabolic syndrome before puberty: Myth or reality? Current Opinion in Endocrine and Metabolic Research. Doi: https://doi.org/10.1016/j.coemr.2020.06.006
Ahmed, M. L., Ong, K. K., & Dunger, D. B. (2009). Childhood obesity and the timing of puberty. Trends Endocrinol Metab, 20(5), 237-242. doi:10.1016/j.tem.2009.02.004.
Ahmed, M. L., Ong, K. K., Morrell, D. J., Cox, L., Drayer, N., Perry, L., .. Dunger, D. B. (1999). Longitudinal study of leptin concentrations during puberty: sex differences and relationship to changes in body composition. J Clin Endocrinol Metab, 84(3), 899-905. Doi: https://doi.org/10.1210/jcem.84.3.5559
Amiel, S. A., Sherwin, R. S., Simonson, D. C., Lauritano, A. A., & Tamborlane, W. V. (1986). Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med, 315(4), 215-219. doi:10.1056/NEJM198607243150402
Argente, J., Barrios, V., Chowen, J., Sinha, M., (1997). Leptin plasma levels in healthy Spanish children and adolescents, children with obesity, and adolescents with anorexia nervosa and bulimia nervosa. J Pediatr, 131(6), 833-838. Doi: https://doi.org/10.1016/S0022-3476(97)70029-5
Arslanian, S., Suprasongsin, C., Kalhan, S. C., Drash, A. L., Brna, R., (1998). Plasma leptin in children: relationship to puberty, gender, body composition, insulin sensitivity, and energy expenditure. Metabolism, 47(3), 309-312. Doi: https://doi.org/10.1016/S0026-0495(98)90262-1
Biro, F. M., Greenspan, L. C., & Galvez, M. P. (2012). Puberty in girls of the 21st century. J Pediatr Adolesc Gynecol, 25(5), 289-294. doi:10.1016/j.jpag.2012.05.009
Blum, W. F., Englaro, P., Hanitsch, S., Juul, A., Hertel, N. T., Müller, J., .  (1997). Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. Journal of Clinical Endocrinology & Metabolism, 82(9), 2904-2910. Doi: https://doi.org/10.1210/jcem.82.9.4251
Boutcher, S., & Dunn, S. (2009). Factors that may impede the weight loss response to exercise‐based interventions. Obesity Reviews, 10(6), 671-680. Doi: https://doi.org/10.1111/j.1467-789X.2009.00621.x
Bray, G. A. (1997). Obesity and reproduction. Human reproduction, 12(suppl 1), 26-32. Doi: https://doi.org/10.1093/humrep/12.suppl_1.26
Burt Solorzano, C. M., & McCartney, C. R. (2010). Obesity and the pubertal transition in girls and boys. Reproduction, 140(3), 399-410. doi:10.1530/REP-10-0119
Buyken, A. E., Karaolis-Danckert, N., & Remer, T. (2009). Association of prepubertal body composition in healthy girls and boys with the timing of early and late pubertal markers. Am J Clin Nutr, 89(1), 221-230. doi:10.3945/ajcn.2008.26733
Caprio, S., Cline, G., Boulware, S., Permanente, C., Shulman, G. I., Sherwin, R. S., & Tamborlane, W. V. (1994). Effects of puberty and diabetes on metabolism of insulin-sensitive fuels. Am J Physiol, 266(6 Pt 1), E885-891. Doi: https://doi.org/10.1152/ajpendo.1994.266.6.E885
Carnier, J., Sanches Pde, L., da Silva, P. L., de Piano, A., Tock, L., Campos, R. M., . . . Damaso, A. R. (2012). Obese adolescents with eating disorders: analysis of metabolic and inflammatory states. Physiol Behav, 105(2), 175-180. doi:10.1016/j.physbeh.2011.08.014
Conwell, L. S., Trost, S. G., Brown, W. J., & Batch, J. A. (2004). Indexes of insulin resistance and secretion in obese children and adolescents a validation study. Diabetes Care, 27(2), 314-319.
Damaso, A. R., de Piano, A., Sanches, P. L., Corgosinho, F., Tock, L., Oyama, L. M., . . . de Mello, M. T. (2011). Hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss. Peptides, 32(7), 1384-1391. doi:10.1016/j.peptides.2011.04.025.
Dardeno, T. A., Chou, S. H., Moon, H.-S., Chamberland, J. P., Fiorenza, C. G., & Mantzoros, C. S. (2010). Leptin in human physiology and therapeutics. Frontiers in neuroendocrinology, 31(3), 377-393. Doi: https://doi.org/10.1016/j.yfrne.2010.06.002
Ertl, T., Funke, S., Sarkany, I., Szabo, I., Rascher, W., Blum, W., & Sulyok, E. (1999). Postnatal changes of leptin levels in full-term and preterm neonates: their relation to intrauterine growth, gender and testosterone. Neonatology, 75(3), 167-176. Doi: https://doi.org/10.1159/000014093
Fernandez-Real, J. M., & Ricart, W. (2003). Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev, 24(3), 278-301. Doi: https://doi.org/10.1210/er.2002-0010
Gesteiro, E., Megía, A., Guadalupe-Grau, A., Fernandez-Veledo, S., Vendrell, J., & González-Gross, M. (2021). Early identification of metabolic syndrome risk: a review of reviews and proposal for defining pre-metabolic syndrome status. Nutrition, Metabolism and Cardiovascular Diseases. Doi: https://doi.org/10.1016/j.numecd.2021.05.022
Goran, M. I., & Gower, B. A. (2001). Longitudinal study on pubertal insulin resistance. Diabetes, 50(11), 2444-2450. Doi: https://doi.org/10.2337/diabetes.50.11.2444
Gueorguiev, M., Góth, M. I., & Korbonits, M. (2001). Leptin and puberty: a review. Pituitary, 4(1-2), 79-86.  Doi: https://doi.org/10.1023/A:1012943029127
Guercio, G., Rivarola, M. A., Chaler, E., Maceiras, M., & Belgorosky, A. (2003). Relationship between the growth hormone/insulin-like growth factor-I axis, insulin sensitivity, and adrenal androgens in normal prepubertal and pubertal girls. J Clin Endocrinol Metab, 88(3), 1389-1393. Doi:  https://doi.org/10.1210/jc.2002-020979
Gungor, N., Saad, R., Janosky, J., & Arslanian, S. (2004). Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents. J Pediatr, 144(1), 47-55. Doi: https://doi.org/10.1016/j.jpeds.2003.09.045
Han, J. C., Lawlor, D. A., & Kimm, S. (2010). Childhood obesity. The Lancet, 375(9727), 1737-1748. Doi: https://doi.org/10.1016/S0140-6736(10)60171-7
Harwood, H. J., Jr. (2012). The adipocyte as an endocrine organ in the regulation of metabolic homeostasis. Neuropharmacology, 63(1), 57-75. doi:10.1016/j.neuropharm.2011.12.010
Hoffman, R. P., Vicini, P., Sivitz, W. I., & Cobelli, C. (2000). Pubertal adolescent male-female differences in insulin sensitivity and glucose effectiveness determined by the one compartment minimal model. Pediatr Res, 48(3), 384-388. doi:10.1203/00006450-200009000-00022
Horlick, M. B., Rosenbaum, M., Nicolson, M., Levine, L. S., Fedun, B., Wang, J., . . . Leibel, R. L. (2000). Effect of puberty on the relationship between circulating leptin and body composition. J Clin Endocrinol Metab, 85(7), 2509-2518.  Doi: https://doi.org/10.1210/jcem.85.7.6689
Huang, A., Reinehr, T., & Roth, C. L. (2020). Connections Between Obesity
and Puberty Invited by Manuel Tena-Sempere, Cordoba. Current Opinion in Endocrine and Metabolic Research.  Doi: https://doi.org/10.1016/j.coemr.2020.08.004
Jeffery, A. N., Metcalf, B. S., Hosking, J., Streeter, A. J., Voss, L. D., & Wilkin, T. J. (2012). Age before stage: insulin resistance rises before the onset of puberty: a 9-year longitudinal study (EarlyBird 26). Diabetes Care, 35(3), 536-541. doi:10.2337/dc11-1281
King, N. A., Caudwell, P., Hopkins, M., Byrne, N. M., Colley, R., Hills, A. P., . . . Blundell, J. E. (2007). Metabolic and behavioral compensatory responses to exercise interventions: barriers to weight loss. Obesity, 15(6), 1373-1383.  Doi: https://doi.org/10.1038/oby.2007.164
Labayen, I., Ortega, F. B., Moreno, L. A., Gonzalez-Gross, M., Jimenez-Pavon, D., Martinez-Gomez, D., . . . Ruiz, J. R. (2013). Physical activity attenuates the negative effect of low birth weight on leptin levels in European adolescents; the HELENA study. Nutr Metab Cardiovasc Dis, 23(4), 344-349. doi:10.1016/j.numecd.2011.12.004
Lee, S. J., Kim, S. H., Park, K. M., Lee, J. H., & Park, J.-W. (2016). Increased obesity resistance and insulin sensitivity in mice lacking the isocitrate dehydrogenase 2 gene. Free Radical Biology and Medicine, 99, 179-188.  Doi: https://doi.org/10.1016/j.freeradbiomed.2016.08.011
Mantzoros, C. S., Flier, J. S., & Rogol, A. D. (1997). A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty. Journal of Clinical Endocrinology & Metabolism, 82(4), 1066-1070. Doi: https://doi.org/10.1210/jcem.82.4.3878
Mantzoros, C. S., Magkos, F., Brinkoetter, M., Sienkiewicz, E., Dardeno, T. A., Kim, S.-Y., . . . Koniaris, A. (2011). Leptin in human physiology and pathophysiology. American Journal of Physiology-Endocrinology and Metabolism, 301(4), E567-E584. Doi: https://doi.org/10.1152/ajpendo.00315.2011
Marroqui, L., Gonzalez, A., Neco, P., Caballero-Garrido, E., Vieira, E., Ripoll, C., . . . Quesada, I. (2012). Role of leptin in the pancreatic beta-cell: effects and signaling pathways. J Mol Endocrinol, 49(1), R9-17. doi:10.1530/JME-12-0025
Marshall, W. A., & Tanner, J. M. (1970). Variations in the pattern of pubertal changes in boys. Archives of disease in childhood, 45(239), 13-23.  Doi: http://dx.doi.org/10.1136/adc.45.239.13
Martinez-Gomez, D., Eisenmann, J. C., Gomez-Martinez, S., Veses, A., Romeo, J., Veiga, O. L., & Marcos, A. (2012). Associations of physical activity and fitness with adipocytokines in adolescents: the AFINOS Study. Nutr Metab Cardiovasc Dis, 22(3), 252-259. doi:10.1016/j.numecd.2010.07.010
Morales, A., Wasserfall, C., Brusko, T., Carter, C., Schatz, D., Silverstein, J., . . . Atkinson, M. (2004). Adiponectin and leptin concentrations may aid in discriminating disease forms in children and adolescents with type 1 and type 2 diabetes. Diabetes Care, 27(8), 2010-2014.  Doi: https://doi.org/10.2337/diacare.27.8.2010
Moran, A., Jacobs, D. R., Jr., Steinberger, J., Steffen, L. M., Pankow, J. S., Hong, C. P., & Sinaiko, A. R. (2008). Changes in insulin resistance and cardiovascular risk during adolescence: establishment of differential risk in males and females. Circulation, 117(18), 2361-2368. doi:10.1161/CIRCULATIONAHA.107.704569
Myers, M. G., Cowley, M. A., & Munzberg, H. (2008). Mechanisms of leptin action and leptin resistance. Annu Rev Physiol, 70, 537-556. doi:10.1146/annurev.physiol.70.113006.100707
Nasreddine, L., Naja, F., Tabet, M., Habbal, M.-Z., El-Aily, A., Haikal, C., . . . Hwalla, N. (2012). Obesity is associated with insulin resistance and components of the metabolic syndrome in Lebanese adolescents. Annals of human biology, 39(2), 122-128. Doi: https://doi.org/10.3109/03014460.2012.655776
Nyambuya, T. M., Dludla, P. V., Mxinwa, V., & Nkambule, B. B. (2019). Obesity-induced inflammation and insulin resistance: A mini-review on T-cells. Metabolism open, 3, 100015. Doi: https://doi.org/10.1016/j.metop.2019.100015
Odle, A. K., Akhter, N., Syed, M. M., Allensworth-James, M. L., Beneš, H., Melgar Castillo, A. I., . . . Childs, G. V. (2018). Leptin regulation of gonadotrope gonadotropin-releasing hormone receptors as a metabolic checkpoint and gateway to reproductive competence. Frontiers in endocrinology, 8, 367. Doi: https://doi.org/10.3389/fendo.2017.00367
Oyama, L. M., Nascimento, C. M. O. d., Carnier, J., Piano, A. d., Tock, L., Sanches, P. d. L., . . . Dâmaso, A. R. (2010). The role of anorexigenic and orexigenic neuropeptides and peripheral signals on quartiles of weight loss in obese adolescents. Neuropeptides, 44(6), 467-474.  Doi: https://doi.org/10.1016/j.npep.2010.07.002
Park, J., Choi, H., Kim, I., Lee, H., Kang, J., & Song, J. (2012). Influence of serum leptin levels on future overweight risk in Korean children. Nutrition, Metabolism and Cardiovascular Diseases, 22(3), 260-268. Doi: https://doi.org/10.1016/j.numecd.2010.08.010
Prado, W. L., Oyama, L. M., Lofrano-Prado, M. C., de Piano, A., Stella, S. G., Nascimento, C. M., . . . Damaso, A. R. (2011). Alterations in downstream mediators involved in central control of eating behavior in obese adolescents submitted to a multidisciplinary therapy. J Adolesc Health, 49(3), 300-305. doi:10.1016/j.jadohealth.2010.12.016
Qasim, A., Mehta, N. N., Tadesse, M. G., Wolfe, M. L., Rhodes, T., Girman, C., & Reilly, M. P. (2008). Adipokines, insulin resistance, and coronary artery calcification. Journal of the American College of Cardiology, 52(3), 231-236. Doi: 10.1016/j.jacc.2008.04.016
Rajpathak, S. N., Gunter, M. J., Wylie‐Rosett, J., Ho, G. Y., Kaplan, R. C., Muzumdar, R., . . . Strickler, H. D. (2009). The role of insulin‐like growth factor‐I and its binding proteins in glucose homeostasis and type 2 diabetes. Diabetes/metabolism research and reviews, 25(1), 3-12. Doi: https://doi.org/10.1002/dmrr.919
Roemmich, J. N., Clark, P. A., Berr, S. S., Mai, V., Mantzoros, C. S., Flier,
J. S., . . . Rogol, A. D. (1998). Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids. Am J Physiol, 275(3 Pt 1), E543-551. Doi: https://doi.org/10.1152/ajpendo.1998.275.3.E543
Rogol, A. D. (2010). Sex steroids, growth hormone, leptin and the pubertal growth spurt. Endocr Dev, 17, 77-85. doi:10.1159/000262530
Roth, C. L., Kratz, M., Ralston, M. M., & Reinehr, T. (2011). Changes in adipose-derived inflammatory cytokines and chemokines after successful lifestyle intervention in obese children. Metabolism, 60(4), 445-452. doi:10.1016/j.metabol.2010.03.023
Rubin, D. A., McMurray, R. G., Harrell, J. S., Hackney, A. C., Thorpe, D. E., & Haqq, A. M. (2008). The association between insulin resistance and cytokines in adolescents: the role of weight status and exercise. Metabolism, 57(5), 683-690. doi:10.1016/j.metabol.2008.01.005
Rutters, F., Nieuwenhuizen, A. G., Verhoef, S. P., Lemmens, S. G., Vogels, N., & Westerterp-Plantenga, M. S. (2009). The relationship between leptin, gonadotropic hormones, and body composition during puberty in a Dutch children cohort. Eur J Endocrinol, 160(6), 973-978. doi:10.1530/EJE-08-0762.
Sengupta, P., Bhattacharya, K., & Dutta, S. (2019). Leptin and male repro duction. Asian Pacific Journal of Reproduction, 8(5), 220. Doi: 10.4103/2305-0500.268143
Sinaiko, A. R., Jacobs, D. R., Jr., Steinberger, J., Moran, A., Luepker, R., Rocchini, A. P., & Prineas, R. J. (2001). Insulin resistance syndrome in childhood: associations of the euglycemic insulin clamp and fasting insulin with fatness and other risk factors. J Pediatr, 139(5), 700-707. doi:10.1067/mpd.2001.118535
Smith, S. R., & Ravussin, E. (2002). Emerging paradigms for understanding fatness and diabetes risk. Curr Diab Rep, 2(3), 223-230.  Doi: https://doi.org/10.1007/s11892-002-0087-1
Vatier, C., Gautier, J. F., & Vigouroux, C. (2012). Therapeutic use of recombinant methionyl human leptin. Biochimie, 94(10), 2116-2125. doi:10.1016/j.biochi.2012.03.013
Wabitsch, M., Blum, W. F., Muche, R., Braun, M., Hube, F., Rascher, W., ... & Hauner, H. (1997). Contribution of androgens to the gender difference in leptin production in obese children and adolescents. The Journal of clinical investigation, 100(4), 808-813. https://www.jci.org/articles/view/119595
Wu, A. H. (2006). Tietz clinical guide to laboratory tests: Saunders/Elsevier St. Louis. eBook ISBN: 9781437719871