Relationship Between Serum Testosterone, Leptin,Interleukin-6 (il-6) Level and Insulin Sensitivity in Non-obese and Obese Male Subjects in Magway Region, Myanmar
Objective: To determine the relationship between insulin resistance and related variables (serum testosterone, interleukin (IL-6) and leptin level) in obese and non-obese healthy subjects. Methods: Community-based crosssectional, analytic study was undertaken in 60 subjects for each obese group (BMI ≥ 30.0 kg/m2) and non-obese group (BMI 18.5 to 24.9 kg/m2) (age;18-45 years) residing in Magway Township from December 2016 to December 2017. Serum insulin, testosterone, IL-6 and leptin levels were measured by enzyme linked immunoassay, and serum fasting glucose was measured by glucose oxidase method. Insulin sensitivity was calculated by HOMA formula (Homeostatic Model Assessment). Results:HOMA-IR, serum leptin and IL-6 level were significantly higher in obese group while serum testosterone level was significantly lower in obese group. There was a significantly correlation between HOMA-IR with leptin (r=0.306, p=0.001), IL-6 (r=0.237, p=0.009) and testosterone (r=-0.209,p=0.02). Moreover, serum leptin was significantly and positively correlated with IL-6 (r=0.391, p<0.001) while serum testosterone was significantly and negatively correlated with leptin (r=-0.408, p<0.001), and IL-6 (r=-0.34, p<0.001).Conclusions:Obese men are more likely to have low testosterone, high inflammatory markers leptin and Il-6, which were associated with decreased insulin sensitivity.
Keywords:Leptin, Testosterone, IL-6, NHOMA-IR, Obesity
 World Health Organization. 2020. Obesity. Retrieved from:https://www.who.int/news room/facts-in-pictures/detail/6-facts-on-obesity
 Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nature Reviews Immunology, 2011, 11(2): 85-97.
 Stelzer I, Zelzer S, Raggam RB, et al. Link between leptin and interleukin-6 levels in the initial phase of obesity related inflammation. Transl Res., 2012,159(2): 118-124.DOI:10.1016/j.trsl.2011.10.001
 Al Maskari MY, Alnaqdy AA. Correlation between Serum Leptin Levels, Body Mass Index and Obesity in Omanis. Sultan Qaboos Univ Med J., 2006,, 6(2):27-31.
 Liu S, Tinker L, Song Y, Rifai N, Bonds DE, Cook NR et al. A prospective study of inflflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women. Arch Intern Med.,2007,167: 1676-1685.
 Kern, P.A., Ranganathan, S., Li, C., Wood, L., Ranganathan, G. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. American Journal of Physiology-Endocrinology And Metabolism, 2001, 280(5):E745-E751.
 Marques-Vidal P, Bastardot F, von Känel R, et al.Association between circulating cytokine levels,diabetes and insulin resistance in a population-based sample (CoLaus study). Clin Endocrinol (Oxf), 2013,78(2): 232-241.DOI: 10.1111/j.1365-2265.2012.04384.x
 Rotter Sopasakis V, Larsson BM, Johansson A,Holmäng A, Smith U. Short-term infusion of interleukin-6 does not induce insulin resistance in vivo or impair insulin signalling in rats. Diabetologia, 2004,47(11): 1879-1887.DOI: 10.1007/s00125-004-1544-y
 Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes, 2002, 51(12): 3391-9.
 Müller G, Ertl J, Gerl M, Preibisch G. Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J Biol Chem., 1997, 272(16): 10585-10593.DOI: 10.1074/jbc.272.16.10585
 Gupta A, Gupta V, Agrawal S, et al. Association between circulating leptin and insulin resistance,the lipid profile, and metabolic risk factors in North Indian adult women. Biosci Trends,2010,4(6): 325-332.
 Naveed AK, Rajput TA, Mahmood N, Malik MM,Kashif F. Effect of Variations in Body Mass Index on Serum Leptin Levels in Pre and Post-Menopausal Women. Global Journal of Health Science, 2010,2(1): 178.
 Huang KC, Lin RC, Kormas N, Lee LT, Chen CY,Gill TP, Caterson ID. Plasma leptin is associated with insulin resistance independent of age, body mass index, fat mass, lipids, and pubertal development in nondiabetic adolescents. International journal of obesity, 2004, 28(4): 470-5.
 Osegbe I, Okpara H, Azinge E. Relationship between serum leptin and insulin resistance among obese Nigerian women. Annals of African medicine, 2016,15(1): 14.
 Zumoff B, Strain GW, Miller LK, Rosner W, Senie R, Seres DS, Rosenfeld RS. 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 & Metabolism, 1990, 71(4): 929-31.
 Khaw KT, Barrett-Connor E. Lower endogenous androgens predict central adiposity in men.Annals of epidemiology. 1992, 2(5): 675-82.
 Gapstur SM, Gann PH, Kopp P, Colangelo L, Longcope C, Liu K. Serum androgen concentrations in young men: A longitudinal analysis of associations with age, obesity, and race.: The CARDIA male hormone study. Cancer Epidemiology and Prevention Biomarkers, 2002, 11(10): 1041-7.
 Xia JW, Tan SJ, Zhang XL, Jun T, Sun XK, Ling W.Correlation of serum testosterone with insulin resistance in elderly male type 2 diabetes mellitus patients with osteoporosis. Journal of diabetes investigation,2015, 6(5): 548-52.
 Bellido T, Jilka RL, Boyce BF, Girasole G, Broxmeyer H, Dalrymple SA, Murray R, Manolagas SC.Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the ndrogen receptor. The Journal of clinical investigation, 1995,95(6): 2886-95.
 George JT, Millar RP, Anderson RA. Hypothesis: kisspeptin mediates male hypogonadism in obesity and type 2 diabetes. Neuroendocrinology, 2010, 91(4):302-307.DOI:10.1159/00029976
 Wei L, Chen Y, Zhang C, Liu M, Xiong H. Leptin induces IL-6 and IL-8 expression through leptin receptor Ob-Rb in human dental pulp fibroblasts. Acta Odontologica Scandinavica, 2019, 77(3):205-12.
 Greco AV, Mingrone G, Giancaterini A, Manco M,Morroni M, Cinti S, Granzotto M, Vettor R,Camastra S, Ferrannini E. Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion.Diabetes, 2002, 51(1): 144-51.
 Chen G, Liu C, Yao J, et al. Overweight, obesity, and their associations with insulin resistance and β-cell function among Chinese: a cross-sectional study in China. Metabolism, 2010, 59(12): 1823-1832.DOI: 10.1016/j.metabol.2010.06.009
 Lim SM, Choi DP, Rhee Y, Kim HC. Association between obesity indices and insulin resistance among healthy Korean adolescents: the JS high school study.PloS one, 2015, 10(5): e0125238.
 Cinti S, Mitchell G, Barbatelli G, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res., 2005, 46(11): 2347-2355.DOI:10.1194/jlr.M500294-JLR200
 Pei-Chi Chan and Po-Shiuan Hsieh. The Role of Adipocyte Hypertrophy and Hypoxia in the Development of Obesity-Associated Adipose Tissue Inflammation and Insulin Resistance, Adiposity - Omics and Molecular Understanding, Jan Oxholm Gordeladze, IntechOpen.DOI:10.5772/65458
 Herder C, Schneitler S, Rathmann W, et al. Lowgrade inflammation, obesity, and insulin resistance in adolescents. J Clin Endocrinol Metab,. 2007, 92(12):4569-4574.DOI:10.1210/jc.2007-0955
 Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med., 1996,334(5): 292-295.DOI:10.1056/NEJM199602013340503
 Kieffer TJ, Habener JF. The adipoinsular axis: effects of leptin on pancreatic beta-cells. Am J hysiol Endocrinol Metab, 2000, 278(1): E1-E14.DOI: 10.1152/ajpendo.2000.278.1.E1
 Ahren BO, Havel PJ. Leptin inhibits insulin secretion induced by cellular cAMP in a pancreatic B cell line (INS-1 cells). American Journal of Physiology-Regulatory, Integrative and Comparative Physiology,1999, 277(4): R959-66.
 Yanase T, Fan W, Kyoya K, Min L, Takayanagi R,Kato S, Nawata H. Androgens and metabolic syndrome: lessons from androgen receptor knock out (ARKO) mice. The Journal of steroid biochemistry and molecular biology, 2008, 109(3-5): 254-7.
 Holmäng A, Björntorp P. The effects of testosterone on insulin sensitivity in male rats. Acta Physiologica Scandinavica, 1992, 146(4): 505-10.
 Kurniawan LB, Adnan E, Mulyono B. Insulin resistance and testosterone level in Indonesian young adult males. Romanian Journal of Internal Medicine,2020, 1.
 Isidori AM, Caprio M, Strollo F, et al. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab., 1999, 84(10): 3673-3680.DOI:10.1210/jcem.84.10.6082
 Leisegang, K., Henkel, R. The in vitro modulation of steroidogenesis by inflammatory cytokines and insulin in TM3 Leydig cells. Reprod Biol Endocrinol,2018, 16(26).https://doi.org/10.1186/s12958-018-0341-2
 Luukkaa V, Pesonen U, Huhtaniemi I, et al. Inverse correlation between serum testosterone and leptin in men. J Clin Endocrinol Metab, 1998, 83(9): 3243-3246.DOI:10.1210/jcem.83.9.5134
 Mohamad NV, Wong SK, Hasan WN, Jolly JJ,Nur-Farhana MF, Ima-Nirwana S, Chin KY. The relationship between circulating testosterone and inflammatory cytokines in men. The Aging Male,2018.
 Sadagurski M, Norquay L, Farhang J, D’Aquino K,Copps K, White MF. Human IL6 enhances leptin action in mice. Diabetologia, 2010, 53(3): 525-535.DOI:10.1007/s00125-009-1580-8
 Vettor R, De Pergola G, Pagano C, et al. Gender differences in serum leptin in obese people: relationships with testosterone, body fat distribution and insulin sensitivity. Eur J Clin Invest., 1997, 27(12):1016-1024.DOI: 10.1046/j.1365-2362.1997.2270773.x
 Tremellen K, McPhee N, Pearce K. Metabolic endotoxaemia related inflammation is associated with hypogonadism in overweight men. Basic Clin Androl.,2017, 27: 5.DOI:10.1186/s12610-017-0049-8
 Neelamekam S, Nurjono M, Lee J. Regulation of interleukin-6 and leptin in schizophrenia patients: a preliminary analysis. Clin Psychopharmacol Neurosci., 2014, 12(3): 209-214.DOI:10.9758/cpn.2014.12.3.209