The Influence of Leptin Resistance on the Development of Childhood Obesity

Authors

  • Stanley Cho Choate Rosemary Hall
  • Dr. Hunter Batchelder

DOI:

https://doi.org/10.47611/jsrhs.v12i2.4339

Keywords:

childhood obesity, obesity, leptin, leptin resistance

Abstract

The rising global prevalence of obesity presents a diminished quality of life and life expectancy. Though a myriad of factors contributes to obesity, one of the leading factors is excessive adipose tissue accumulation increases the body’s production of the leptin satiety hormone resulting in leptin resistance. Leptin resistance results in increased vulnerability to obesity through improper regulation of insulin, a decline in metabolic functions, and decreased sex hormone levels. Leptin resistance is treated with natural treatments, leptin replacement therapy, testosterone replacement therapy, and insulin-sensitizing drugs, although all are met with limited results. Since leptin vastly affects sex hormone levels, leptin resistance has an adverse effect on obese children and adolescents. In this review, we examine the causes of leptin resistance, treatments for leptin resistance, and the effect of leptin resistance on childhood development.

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Author Biographies

Stanley Cho, Choate Rosemary Hall

Stanley Cho is a sophomore attending Choate Rosemary Hall in Wallingford, CT. Despite being a high school student, his scientific repertoire includes accolades from the Korean Science and Engineering Fair (KSEF), Connecticut Science and Engineering Fair (CSEF), and Genius Olympiad. 

Dr. Hunter Batchelder

Dr. Batchelder received a PhD in Organic Chemistry and a Masters in Chemistry from Johns Hopkins University. He has an Honors Bachelor of Science in Biological Chemistry from University of Toronto. He was a Teaching Assistant for numerous classes during his time at JHU, and he also held a Teaching Assistant leadership role in many of these classes. Beyond his PhD, he has also been mentoring high school students on projects where they write a review on a current chemistry topic in the literature. He relays the principles of how to navigate the research literature landscape, how to compose and write a scientific article, and how to do it all while managing deadlines. reality. As an educator, he has extensive teaching and researching experiences and focuses on translating basic scientific knowledge into practical applications in hopes to engage students and develop an appreciation for the natural world.

References or Bibliography

Arora, H., Zuttion, M. S. S. R., Nahar, B., Lamb, D., Hare, J. M., & Ramasamy, R. (2019). Subcutaneous Leydig Stem Cell Autograft: A Promising Strategy to Increase Serum Testosterone. Stem Cells Translational Medicine, 8(1), 58–65. https://doi.org/10.1002/sctm.18-0069

Bliss, S. P., Navratil, A. M., Xie, J., & Roberson, M. S. (2010). GnRH signaling, the gonadotrope and endocrine control of fertility. Frontiers in Neuroendocrinology, 31(3), 322–340. https://doi.org/10.1016/j.yfrne.2010.04.002

Blüher, M. (2019). Obesity: global epidemiology and pathogenesis. Nature Reviews. Endocrinology, 15(5), 288–298. https://doi.org/10.1038/s41574-019-0176-8

Booth, A., Magnuson, A., Fouts, J., & Foster, M. T. (2016). Adipose tissue: an endocrine organ playing a role in metabolic regulation. In Hormone Molecular Biology and Clinical Investigation (Vol. 26, Issue 1). https://doi.org/10.1515/hmbci-2015-0073

CDC. (2022, July 14). Why It Matters. Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/about-obesity/why-it-matters.html

Clayton, P. E., Gill, M. S., Hall, C. M., Tillmann, V., Whatmore, A. J., & Price, D. A. (1997). Serum leptin through childhood and adolescence. Clinical Endocrinology, 46(6), 727–733. https://doi.org/10.1046/j.1365-2265.1997.2081026.x

Covey, S. D., Wideman, R. D., McDonald, C., Unniappan, S., Huynh, F., Asadi, A., Speck, M., Webber, T., Chua, S. C., & Kieffer, T. J. (2006). The pancreatic beta cell is a key site for mediating the effects of leptin on glucose homeostasis. Cell Metabolism, 4(4), 291–302. https://doi.org/10.1016/j.cmet.2006.09.005

Di Spiezio, A., Sandin, E. S., Dore, R., Müller-Fielitz, H., Storck, S. E., Bernau, M., Mier, W., Oster, H., Jöhren, O., Pietrzik, C. U., Lehnert, H., & Schwaninger, M. (2018). The LepR-mediated leptin transport across brain barriers controls food reward. Molecular Metabolism, 8, 13–22. https://doi.org/10.1016/j.molmet.2017.12.001

Dumesic, D. A., Hoyos, L. R., Chazenbalk, G. D., Naik, R., Padmanabhan, V., & Abbott, D. H. (2020). Mechanisms of intergenerational transmission of polycystic ovary syndrome. Reproduction , 159(1), R1–R13. https://doi.org/10.1530/REP-19-0197

Friedman, J. M., & Halaas, J. L. (1998). Leptin and the regulation of body weight in mammals. Nature, 395(6704), 763–770. https://doi.org/10.1038/27376

Geffner, M. E. (1996). The growth without growth hormone syndrome. Endocrinology and Metabolism Clinics of North America, 25(3), 649–663. https://doi.org/10.1016/s0889-8529(05)70345-5

Gruzdeva, O., Borodkina, D., Uchasova, E., Dyleva, Y., & Barbarash, O. (2019). Leptin resistance: underlying mechanisms and diagnosis. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 12, 191–198. https://doi.org/10.2147/DMSO.S182406

Guercio, G., Saraco, N., Costanzo, M., Marino, R., Ramirez, P., Berensztein, E., Rivarola, M. A., & Belgorosky, A. (2020). Estrogens in Human Male Gonadotropin Secretion and Testicular Physiology From Infancy to Late Puberty. Frontiers in Endocrinology, 11, 72. https://doi.org/10.3389/fendo.2020.00072

Hagan, S., & Niswender, K. D. (2012). Neuroendocrine regulation of food intake. Pediatric Blood & Cancer, 58(1), 149–153. https://doi.org/10.1002/pbc.23376

Halleux, C. M. (1998). Multihormonal Control of ob Gene Expression and Leptin Secretion from Cultured Human Visceral Adipose Tissue: Increased Responsiveness to Glucocorticoids in Obesity. In Journal of Clinical Endocrinology & Metabolism (Vol. 83, Issue 3, pp. 902–910). https://doi.org/10.1210/jc.83.3.902

Harris, R. B. S. (2014). Direct and indirect effects of leptin on adipocyte metabolism. Biochimica et Biophysica Acta, 1842(3), 414–423. https://doi.org/10.1016/j.bbadis.2013.05.009

Hebebrand, J., Muller, T. D., Holtkamp, K., & Herpertz-Dahlmann, B. (2007). The role of leptin in anorexia nervosa: clinical implications. Molecular Psychiatry, 12(1), 23–35. https://doi.org/10.1038/sj.mp.4001909

Isidori, A. M., Caprio, M., Strollo, F., Moretti, C., Frajese, G., Isidori, A., & Fabbri, A. (1999). Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. The Journal of Clinical Endocrinology and Metabolism, 84(10), 3673–3680. https://doi.org/10.1210/jcem.84.10.6082

Israel, D., & Chua, S., Jr. (2010). Leptin receptor modulation of adiposity and fertility. Trends in Endocrinology and Metabolism: TEM, 21(1), 10–16. https://doi.org/10.1016/j.tem.2009.07.004

Kansra, A. R., Lakkunarajah, S., & Jay, M. S. (2020). Childhood and Adolescent Obesity: A Review. Frontiers in Pediatrics, 8, 581461. https://doi.org/10.3389/fped.2020.581461

Kelly, D. M., & Jones, T. H. (2015). Testosterone and obesity. Obesity Reviews: An Official Journal of the International Association for the Study of Obesity, 16(7), 581–606. https://doi.org/10.1111/obr.12282

Kershaw, E. E., & Flier, J. S. (2004). Adipose tissue as an endocrine organ. The Journal of Clinical Endocrinology and Metabolism, 89(6), 2548–2556. https://doi.org/10.1210/jc.2004-0395

Khodamoradi, K., Khosravizadeh, Z., Seetharam, D., Mallepalli, S., Farber, N., & Arora, H. (2022). The role of leptin and low testosterone in obesity. International Journal of Impotence Research. https://doi.org/10.1038/s41443-022-00534-y

Koerner, A., Kratzsch, J., & Kiess, W. (2005). Adipocytokines: leptin—the classical, resistin—the controversical, adiponectin—the promising, and more to come. Best Practice & Research. Clinical Endocrinology & Metabolism, 19(4), 525–546. https://doi.org/10.1016/j.beem.2005.07.008

Licinio, J., Negrão, A. B., Mantzoros, C., Kaklamani, V., Wong, M. L., Bongiorno, P. B., Negro, P. P., Mulla, A., Veldhuis, J. D., Cearnal, L., Flier, J. S., & Gold, P. W. (1998). Sex differences in circulating human leptin pulse amplitude: clinical implications. The Journal of Clinical Endocrinology and Metabolism, 83(11), 4140–4147. https://doi.org/10.1210/jcem.83.11.5291

Lin, H.-Y., Xu, Q., Yeh, S., Wang, R.-S., Sparks, J. D., & Chang, C. (2005). Insulin and leptin resistance with hyperleptinemia in mice lacking androgen receptor. Diabetes, 54(6), 1717–1725. https://doi.org/10.2337/diabetes.54.6.1717

Liu, J., Yang, X., Yu, S., & Zheng, R. (2018). The Leptin Resistance. In Q. Wu & R. Zheng (Eds.), Neural Regulation of Metabolism (pp. 145–163). Springer Singapore. https://doi.org/10.1007/978-981-13-1286-1_8

Martin, S. S., Qasim, A., & Reilly, M. P. (2008). Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. Journal of the American College of Cardiology, 52(15), 1201–1210. https://doi.org/10.1016/j.jacc.2008.05.060

McConway, M. G., Johnson, D., Kelly, A., Griffin, D., Smith, J., & Wallace, A. M. (2000). Differences in circulating concentrations of total, free and bound leptin relate to gender and body composition in adult humans. Annals of Clinical Biochemistry, 37 ( Pt 5), 717–723. https://doi.org/10.1258/0004563001899771

Milaneschi, Y., Simonsick, E. M., Vogelzangs, N., Strotmeyer, E. S., Yaffe, K., Harris, T. B., Tolea, M. I., Ferrucci, L., Penninx, B. W. J. H., & Health, Aging, and Body Composition Study. (2012). Leptin, abdominal obesity, and onset of depression in older men and women. The Journal of Clinical Psychiatry, 73(9), 1205–1211. https://doi.org/10.4088/JCP.11m07552

Montague, C. T., Prins, J. B., Sanders, L., Digby, J. E., & O’Rahilly, S. (1997). Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. In Diabetes (Vol. 46, Issue 3, pp. 342–347). https://doi.org/10.2337/diabetes.46.3.342

Moon, H.-S., Matarese, G., Brennan, A. M., Chamberland, J. P., Liu, X., Fiorenza, C. G., Mylvaganam, G. H., Abanni, L., Carbone, F., Williams, C. J., De Paoli, A. M., Schneider, B. E., & Mantzoros, C. S. (2011). Efficacy of metreleptin in obese patients with type 2 diabetes: cellular and molecular pathways underlying leptin tolerance. Diabetes, 60(6), 1647–1656. https://doi.org/10.2337/db10-1791

Myers, M. G., Jr, Leibel, R. L., Seeley, R. J., & Schwartz, M. W. (2010). Obesity and leptin resistance: distinguishing cause from effect. Trends in Endocrinology and Metabolism: TEM, 21(11), 643–651. https://doi.org/10.1016/j.tem.2010.08.002

Palmer, N. O., Bakos, H. W., Fullston, T., & Lane, M. (2012). Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis, 2(4), 253–263. https://doi.org/10.4161/spmg.21362

Pasquali, R., Pelusi, C., Genghini, S., Cacciari, M., & Gambineri, A. (2003). Obesity and reproductive disorders in women. Human Reproduction Update, 9(4), 359–372. https://doi.org/10.1093/humupd/dmg024

Paz-Filho, G., Mastronardi, C. A., & Licinio, J. (2015). Leptin treatment: facts and expectations. Metabolism: Clinical and Experimental, 64(1), 146–156. https://doi.org/10.1016/j.metabol.2014.07.014

Paz-Filho, G., Wong, M.-L., & Licinio, J. (2011). Ten years of leptin replacement therapy. Obesity Reviews: An Official Journal of the International Association for the Study of Obesity, 12(5), e315–e323. https://doi.org/10.1111/j.1467-789X.2010.00840.x

Revelo, X. S., Luck, H., Winer, S., & Winer, D. A. (2014). Morphological and inflammatory changes in visceral adipose tissue during obesity. Endocrine Pathology, 25(1), 93–101. https://doi.org/10.1007/s12022-013-9288-1

Ronveaux, C. C., Tomé, D., & Raybould, H. E. (2015). Glucagon-like peptide 1 interacts with ghrelin and leptin to regulate glucose metabolism and food intake through vagal afferent neuron signaling. The Journal of Nutrition, 145(4), 672–680. https://doi.org/10.3945/jn.114.206029

Saad, M. F., Damani, S., Gingerich, R. L., Riad-Gabriel, M. G., Khan, A., Boyadjian, R., Jinagouda, S. D., el-Tawil, K., Rude, R. K., & Kamdar, V. (1997). Sexual dimorphism in plasma leptin concentration. The Journal of Clinical Endocrinology and Metabolism, 82(2), 579–584. https://doi.org/10.1210/jcem.82.2.3739

Santoro, A., Mattace Raso, G., & Meli, R. (2015). Drug targeting of leptin resistance. Life Sciences, 140, 64–74. https://doi.org/10.1016/j.lfs.2015.05.012

Shalitin, S., & Phillip, M. (2003). Role of obesity and leptin in the pubertal process and pubertal growth—a review. International Journal of Obesity, 27(8), 869–874. https://doi.org/10.1038/sj.ijo.0802328

Shephard, R. J. (2011). Body-Mass Index and Mortality among 1.46 Million White Adults. In Yearbook of Sports Medicine (Vol. 2011, pp. 163–165). https://doi.org/10.1016/j.yspm.2011.03.017

Sorva, R. (1988). Children with craniopharyngioma. Early growth failure and rapid postoperative weight gain. Acta Paediatrica Scandinavica, 77(4), 587–592. https://doi.org/10.1111/j.1651-2227.1988.tb10705.x

Vignolo, M., Naselli, A., Di Battista, E., Mostert, M., & Aicardi, G. (1988). Growth and development in simple obesity. European Journal of Pediatrics, 147(3), 242–244. https://doi.org/10.1007/BF00442687

Wang, B., Chandrasekera, P. C., & Pippin, J. J. (2014). Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes. Current Diabetes Reviews, 10(2), 131–145. https://doi.org/10.2174/1573399810666140508121012

Wang, C., Jackson, G., Jones, T. H., Matsumoto, A. M., Nehra, A., Perelman, M. A., Swerdloff, R. S., Traish, A., Zitzmann, M., & Cunningham, G. (2011). Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care, 34(7), 1669–1675. https://doi.org/10.2337/dc10-2339

Whitlock, G., Lewington, S., Sherliker, P., & Clarke, R. (2009). Prospective Studies Collaboration: Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. The Lancet.

World Health Organization. (2022). Retrieved December 3, 2022, from https://www.who.int/health-topics/obesity

Xu, L., & Ota, T. (2018). Emerging roles of SGLT2 inhibitors in obesity and insulin resistance: Focus on fat browning and macrophage polarization. Adipocyte, 7(2), 121–128. https://doi.org/10.1080/21623945.2017.1413516

Zhai, L., Zhao, J., Zhu, Y., Liu, Q., Niu, W., Liu, C., & Wang, Y. (2018). Downregulation of leptin receptor and kisspeptin/GPR54 in the murine hypothalamus contributes to male hypogonadism caused by high-fat diet-induced obesity. Endocrine, 62(1), 195–206. https://doi.org/10.1007/s12020-018-1646-9

Zhao, J., Zhai, L., Liu, Z., Wu, S., & Xu, L. (2014). Leptin level and oxidative stress contribute to obesity-induced low testosterone in murine testicular tissue. Oxidative Medicine and Cellular Longevity, 2014, 190945. https://doi.org/10.1155/2014/190945

Zumoff, B., Strain, G. W., Miller, L. K., Rosner, W., Senie, R., Seres, D. S., & Rosenfeld, R. S. (1990). Plasma free and non-sex-hormone-binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity. The Journal of Clinical Endocrinology and Metabolism, 71(4), 929–931. https://doi.org/10.1210/jcem-71-4-929

Published

05-31-2023

How to Cite

Cho, S., & Batchelder, H. (2023). The Influence of Leptin Resistance on the Development of Childhood Obesity. Journal of Student Research, 12(2). https://doi.org/10.47611/jsrhs.v12i2.4339

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Section

HS Review Articles