UCP2, SHBG, Leptin, and T3 Levels are Associated with Resting Energy Expenditure in Obese Women

Author(s): Somaye Ahmadi, Hamideh Pishva*, Mohammad R. Eshraghian, Mehdi Hedayati

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 20 , Issue 2 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Objective: The aim of this study was to investigate the association of Sex Hormone Binding Globulin (SHBG) with leptin, Triidothyronine (T3), and Uncoupling Protein 2 (UCP2) in obese women with low and normal Resting Energy Expenditure (REE) and to determine the role of these factors in the regulation of REE in obese women.

Method: A total 49 subjects (25-50 years old) were selected. Anthropometric and body composition parameters and resting energy expenditure were measured. Fasting circulating leptin, T3, SHBG and UCP2 levels were measured. Subjects were divided into three groups: Group І (BMI>30 and low resting energy expenditure, 16 subjects), group II (BMI>30 and normal resting energy expenditure, 17 subjects), and group ІІІ (control group, 16 non-obese subjects).

Result: It was found that obese subjects who had higher SHBG and leptin levels were at risk for high levels of UCP2. A significant association was found between T3 and REE. Obese subjects with higher concentrations of UCP2 and SHBG had decreased resting energy expenditure. A significant association was observed between SHBG and leptin in group І (r=0.90, p<0.0001) and group ІІ (r=0.83, p<0.0001). Moreover, a significant association was found between T3 and SHBG in group І (r=-0.69, P=0.003).

Conclusion: Changes of the UCP2, leptin, and thyroid hormone (T3) levels may be related to SHBG levels. Thus, lower leptin and T3 levels may decrease SHBG in obese women. Therefore, lower SHBG, leptin, T3 and UCP2 levels may decrease the REE level in obese women.

Keywords: Obesity, resting energy expenditure, UCP2, sex hormone binding globulin, leptin, body mass index.

Obesity: preventing and managing the global epidemic, World Health Organization. 2000.
Veghari, G.; Sedaghat, M.; Banihashem, S.; Moharloei, P.; Angizeh, A.; Tazik, E.; Moghaddami, A. Trends in waist circumference and central obesity in adults, northern iran. Oman Med. J., 2012, 27(1), 50-53.
[http://dx.doi.org/10.5001/omj.2012.10] [PMID: 22359726]
SZCZĘSNA, A.; MĘCZEKALSKI, B. Obesity and polycystic ovary syndrome. Archives of perinatal medicine, 2012, 184, 214- 221..
Barbe, P.; Millet, L.; Larrouy, D.; Galitzky, J.; Berlan, M.; Louvet, J-P.; Langin, D. Uncoupling protein-2 messenger ribonucleic acid expression during very-low-calorie diet in obese premenopausal women. J. Clin. Endocrinol. Metab., 1998, 83(7), 2450-2453.
[http://dx.doi.org/10.1210/jcem.83.7.4962] [PMID: 9661627]
Browning, M.G.; Evans, R.K. The contribution of fat-free mass to resting energy expenditure: implications for weight loss strategies in the treatment of adolescent obesity. Int. J. Adolesc. Med. Health, 2015, 27(3), 241-246.
[http://dx.doi.org/10.1515/ijamh-2014-0036] [PMID: 25470604]
Camps, S.; Verhoef, S.; Westerterp, K. Leptin and energy restriction induced adaptations in resting energy expenditure and physical activity. How humans economize, 2015, 79
Day, D.S.; Gozansky, W.S.; Van Pelt, R.E.; Schwartz, R.S.; Kohrt, W.M. Sex hormone suppression reduces resting energy expenditure and β-adrenergic support of resting energy expenditure. J. Clin. Endocrinol. Metab., 2005, 90(6), 3312-3317.
[http://dx.doi.org/10.1210/jc.2004-1344] [PMID: 15741268]
Rosenbaum, M.; Goldsmith, R.; Bloomfield, D.; Magnano, A.; Weimer, L.; Heymsfield, S.; Gallagher, D.; Mayer, L.; Murphy, E.; Leibel, R.L. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J. Clin. Invest., 2005, 115(12), 3579-3586.
[http://dx.doi.org/10.1172/JCI25977] [PMID: 16322796]
Paxton, R.J.; King, D.W.; Garcia-Prieto, C.; Connors, S.K.; Hernandez, M.; Gor, B.J.; Jones, L.A. Associations between body size and serum estradiol and sex hormone-binding globulin levels in premenopausal African American women. J. Clin. Endocrinol. Metab., 2013, 98(3), E485-E490.
[http://dx.doi.org/10.1210/jc.2012-2782] [PMID: 23408572]
Morisset, A-S.; Blouin, K.; Tchernof, A. Impact of diet and adiposity on circulating levels of sex hormone-binding globulin and androgens. Nutr. Rev., 2008, 66(9), 506-516.
[http://dx.doi.org/10.1111/j.1753-4887.2008.00083.x] [PMID: 18752474]
Rosner, W. Free estradiol and sex hormone-binding globulin. Steroids, 2015, 99(Pt A), 113-116.
[http://dx.doi.org/10.1016/j.steroids.2014.08.005] [PMID: 25453337]
Pasquali, R.; Vicennati, V.; Bertazzo, D.; Casimirri, F.; Pascal, G.; Tortelli, O.; Labate, A.M.M. Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status. Metabolism, 1997, 46(1), 5-9.
[http://dx.doi.org/10.1016/S0026-0495(97)90159-1] [PMID: 9005961]
Hautanen, A. Synthesis and regulation of sex hormone-binding globulin in obesity. Int. J. Obes. Relat. Metab. Disord., 2000, 24(Suppl. 2), S64-S70.
[http://dx.doi.org/10.1038/sj.ijo.0801281] [PMID: 10997612]
Strata, A.; Ugolotti, G.; Contini, C.; Magnati, G.; Pugnoli, C.; Tirelli, F.; Zuliani, U. Thyroid and obesity: survey of some function tests in a large obese population. Int. J. Obes., 1978, 2(3), 333-340.
[PMID: 82549]
Sarne, D.H.; Refetoff, S.; Rosenfield, R.L.; Farriaux, J.P. Sex hormone-binding globulin in the diagnosis of peripheral tissue resistance to thyroid hormone: the value of changes after short term triiodothyronine administration. J. Clin. Endocrinol. Metab., 1988, 66(4), 740-746.
[http://dx.doi.org/10.1210/jcem-66-4-740] [PMID: 3346353]
de Nayer, P.; Lambot, M.P.; Desmons, M.C.; Rennotte, B.; Malvaux, P.; Beckers, C. Sex hormone-binding protein in hyperthyroxinemic patients: a discriminator for thyroid status in thyroid hormone resistance and familial dysalbuminemic hyperthyroxinemia. J. Clin. Endocrinol. Metab., 1986, 62(6), 1309-1312.
[http://dx.doi.org/10.1210/jcem-62-6-1309] [PMID: 3084540]
Lu, R-H.; Liang, X-F.; Wang, M.; Zhou, Y.; Bai, X-L.; He, Y. The role of leptin in lipid metabolism in fatty degenerated hepatocytes of the grass carp Ctenopharyngodon idellus. Fish Physiol. Biochem., 2012, 38(6), 1759-1774.
[http://dx.doi.org/10.1007/s10695-012-9673-6] [PMID: 22760861]
Scarpace, P.J.; Nicolson, M.; Matheny, M. UCP2, UCP3 and leptin gene expression: modulation by food restriction and leptin. J. Endocrinol., 1998, 159(2), 349-357.
[http://dx.doi.org/10.1677/joe.0.1590349] [PMID: 9795377]
Harris, J.A.; Benedict, F.G. A biometric study of human basal metabolism. Proc. Natl. Acad. Sci. USA, 1918, 4(12), 370-373.
[http://dx.doi.org/10.1073/pnas.4.12.370] [PMID: 16576330]
Weinsier, R.L.; Hunter, G.R.; Zuckerman, P.A.; Darnell, B.E. Low resting and sleeping energy expenditure and fat use do not contribute to obesity in women. Obes. Res., 2003, 11(8), 937-944.
[http://dx.doi.org/10.1038/oby.2003.129] [PMID: 12917497]
Brúsik, M.; Ukropec, J.; Joppa, P.; Ukropcová, B.; Skyba, P.; Baláž, M.; Pobeha, P.; Kurdiová, T.; Klimeš, I.; Tkáč, I.; Gašperíková, D.; Tkáčová, R. Circulatory and adipose tissue leptin and adiponectin in relationship to resting energy expenditure in patients with chronic obstructive pulmonary disease. Physiol. Res., 2012, 61(5), 469-480.
[PMID: 22881231]
Tufano, A.; Marzo, P.; Enrini, R.; Morricone, L.; Caviezel, F.; Ambrosi, B. Anthropometric, hormonal and biochemical differences in lean and obese women before and after menopause. J. Endocrinol. Invest., 2004, 27(7), 648-653.
[http://dx.doi.org/10.1007/BF03347497] [PMID: 15505988]
Dumesic, D.A.; Lesnick, T.G.; Abbott, D.H. Increased adiposity enhances intrafollicular estradiol levels in normoandrogenic ovulatory women receiving gonadotropin-releasing hormone analog/recombinant human follicle-stimulating hormone therapy for in vitro fertilization. J. Clin. Endocrinol. Metab., 2007, 92(4), 1438-1441.
[http://dx.doi.org/10.1210/jc.2006-2161] [PMID: 17244784]
Stattin, P.; Söderberg, S.; Hallmans, G.; Bylund, A.; Kaaks, R.; Stenman, U.H.; Bergh, A.; Olsson, T. Leptin is associated with increased prostate cancer risk: a nested case-referent study. J. Clin. Endocrinol. Metab., 2001, 86(3), 1341-1345.
[http://dx.doi.org/10.1210/jc.86.3.1341] [PMID: 11238530]
Anderson, D.C. Sex-hormone-binding globulin. Clin. Endocrinol. (Oxf.), 1974, 3(1), 69-96.
[http://dx.doi.org/10.1111/j.1365-2265.1974.tb03298.x] [PMID: 4134992]
Codaccioni, J.L.; Orgiazzi, J.; Blanc, P.; Pugeat, M.; Roulier, R.; Carayon, P. Lasting remissions in patients treated for Graves’ hyperthyroidism with propranolol alone: a pattern of spontaneous evolution of the disease. J. Clin. Endocrinol. Metab., 1988, 67(4), 656-662.
[http://dx.doi.org/10.1210/jcem-67-4-656] [PMID: 3417846]
Brenta, G.; Schnitman, M.; Gurfinkiel, M.; Damilano, S.; Pierini, A.; Sinay, I.; Pisarev, M.A. Variations of sex hormone-binding globulin in thyroid dysfunction. Thyroid, 1999, 9(3), 273-277.
[http://dx.doi.org/10.1089/thy.1999.9.273] [PMID: 10211604]
Siemińska, L.; Foltyn, W.; Głogowska-Szeląg, J.; Kajdaniuk, D.; Marek, B.; Nowak, M.; Walczak, K.; Kos-Kudła, B. Relationships between adiponectin, sex hormone binding globulin and insulin resistance in hyperthyroid Graves’ disease women. Endokrynol. Pol., 2013, 64(1), 26-29.
[PMID: 23450444]
Wildman, R.P.; Wang, D.; Fernandez, I.; Mancuso, P.; Santoro, N.; Scherer, P.E.; Sowers, M.R. Associations of testosterone and sex hormone binding globulin with adipose tissue hormones in midlife women. Obesity (Silver Spring), 2013, 21(3), 629-636.
[http://dx.doi.org/10.1002/oby.20256] [PMID: 23592672]
Karim, R.; Stanczyk, F.Z.; Brinton, R.D.; Rettberg, J.; Hodis, H.N.; Mack, W.J. Association of endogenous sex hormones with adipokines and ghrelin in postmenopausal women. J. Clin. Endocrinol. Metab., 2015, 100(2), 508-515.
[http://dx.doi.org/10.1210/jc.2014-1839] [PMID: 25405497]
Laughlin, G.A.; Morales, A.J.; Yen, S.S. Serum leptin levels in women with polycystic ovary syndrome: the role of insulin resistance/hyperinsulinemia. J. Clin. Endocrinol. Metab., 1997, 82(6), 1692-1696.
[http://dx.doi.org/10.1210/jc.82.6.1692] [PMID: 9177365]
Rouru, J.; Anttila, L.; Koskinen, P.; Penttilä, T-A.; Irjala, K.; Huupponen, R.; Koulu, M. Serum leptin concentrations in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 1997, 82(6), 1697-1700.
[http://dx.doi.org/10.1210/jcem.82.6.3996] [PMID: 9177366]
Hautanen, A. Synthesis and regulation of sex hormone-binding globulin in obesity. Int. J. Obes. Relat. Metab. Disord., 2000, 24(Suppl. 2), S64-S70.
[http://dx.doi.org/10.1038/sj.ijo.0801281] [PMID: 10997612]
Shimizu, H.; Shimomura, Y.; Nakanishi, Y.; Futawatari, T.; Ohtani, K.; Sato, N.; Mori, M. Estrogen increases in vivo leptin production in rats and human subjects. J. Endocrinol., 1997, 154(2), 285-292.
[http://dx.doi.org/10.1677/joe.0.1540285] [PMID: 9291839]
Elbers, J.M.; Asscheman, H.; Seidell, J.C.; Frölich, M.; Meinders, A.E.; Gooren, L.J. Reversal of the sex difference in serum leptin levels upon cross-sex hormone administration in transsexuals. J. Clin. Endocrinol. Metab., 1997, 82(10), 3267-3270.
[http://dx.doi.org/10.1210/jc.82.10.3267] [PMID: 9329351]
Ježek, P. Possible physiological roles of mitochondrial uncoupling proteins--UCPn. Int. J. Biochem. Cell Biol., 2002, 34(10), 1190-1206.
[http://dx.doi.org/10.1016/S1357-2725(02)00061-4] [PMID: 12127570]
Scarpace, P.J.; Matheny, M.; Moore, R.L.; Kumar, M.V. Modulation of uncoupling protein 2 and uncoupling protein 3: regulation by denervation, leptin and retinoic acid treatment. J. Endocrinol., 2000, 164(3), 331-337.
[http://dx.doi.org/10.1677/joe.0.1640331] [PMID: 10694373]
Teirmaa, T.; Luukkaa, V.; Rouru, J.; Koulu, M.; Huupponen, R. Correlation between circulating leptin and luteinizing hormone during the menstrual cycle in normal-weight women. Eur. J. Endocrinol., 1998, 139(2), 190-194.
[http://dx.doi.org/10.1530/eje.0.1390190] [PMID: 9724075]
Svendsen, O.L.; Hassager, C.; Christiansen, C. Impact of regional and total body composition and hormones on resting energy expenditure in overweight postmenopausal women. Metabolism, 1993, 42(12), 1588-1591.
[http://dx.doi.org/10.1016/0026-0495(93)90155-H] [PMID: 8246774]
Choudhury, F.; Bernstein, L.; Hodis, H.N.; Stanczyk, F.Z.; Mack, W.J. Physical activity and sex hormone levels in estradiol- and placebo-treated postmenopausal women. Menopause, 2011, 18(10), 1079-1086.
[http://dx.doi.org/10.1097/gme.0b013e318215f7bd] [PMID: 21646925]
Keller, J.L.; Casson, P.R.; Toth, M.J. Relationship of androgens to body composition, energy and substrate metabolism and aerobic capacity in healthy, young women. Steroids, 2011, 76(12), 1247-1251.
[http://dx.doi.org/10.1016/j.steroids.2011.06.001] [PMID: 21729710]
Nagy, T.R.; Gower, B.A.; Shewchuk, R.M.; Goran, M.I. Serum leptin and energy expenditure in children. J. Clin. Endocrinol. Metab., 1997, 82(12), 4149-4153.
[http://dx.doi.org/10.1210/jc.82.12.4149] [PMID: 9398730]
Roberts, S.B.; Nicholson, M.; Staten, M.; Dallal, G.E.; Sawaya, A.L.; Heyman, M.B.; Fuss, P.; Greenberg, A.S. Relationship between circulating leptin and energy expenditure in adult men and women aged 18 years to 81 years. Obes. Res., 1997, 5(5), 459-463.
[http://dx.doi.org/10.1002/j.1550-8528.1997.tb00671.x] [PMID: 9385622]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 23 July, 2019
Page: [234 - 241]
Pages: 8
DOI: 10.2174/1871530319666190723154147
Price: $65

Article Metrics

PDF: 18