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Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution

International Journal of Obesity volume 25, pages 1365–1371 (2001)Cite this article

Abstract

BACKGROUND: Circulating concentrations of leptin normalized to total adipose tissue mass are significantly greater in females than in males. Rates of leptin expression (per gram of adipose tissue) are significantly greater in subcutaneous (SAT) than visceral (VAT) adipose tissue and the relative amount of fat stored as SAT vs VAT is significantly greater in pre-menopausal females than in males. Gender-related differences in the relative amounts of SAT and VAT may account for the greater circulating leptin concentration relative to fat-mass in females than males.

METHODS: We examined body composition and anatomic fat distribution by dual energy X-ray-absorptiometry (DEXA) and magnetic resonance imaging (MRI), and post-absorptive circulating concentrations of leptin and insulin in 58 subjects (26 females, 32 males). Stepwise multiple linear regression analyses, treating gender as a dichotomous variable, were performed to determine inter-relationships among leptin concentrations and insulin concentrations, VAT and SAT.

RESULTS: Body composition by DEXA and MRI were highly correlated (r2=0.97, P<0.0001). There were significant gender effects on leptin/total fat mass (males, 0.17±0.01 ng/ml/kg; females, 0.49±0.05 ng/ml/kg; P<0.0001) and relative amounts of fat in SAT and VAT depots (ratio of SAT/VAT; males, 12.3±1.5; females, 32.9±3.2; P<0.0001). Circulating leptin concentration was significantly correlated with insulin concentration (P=0.001), SAT (P<0.0001) and gender (P=0.033). Circulating concentrations of insulin were significantly correlated with VAT, but not SAT, in males and with SAT, but not VAT, in females.

CONCLUSIONS: The sexual dimorphism in the relationship between leptin and adipose tissue mass cannot be explained by differences in the relative amounts of VAT and SAT. Thus, the sexual dimorphism in plasma leptin concentration appears to reflect, at least in part, effects of circulating concentrations of gonadal steroids (especially androgens) and/or primary genetic differences that are independent of amounts of VAT or SAT.

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References

  1. Rosenbaum M, Nicolson M, Hirsch J, Murphy E, Chu F, Leibel R . Effects of weight change on plasma leptin concentrations and energy expenditure J Clin Endocrinol Metab 1997 82: 3647–3654.

    CAS  PubMed  Google Scholar 

  2. Rosenbaum M, Nicolson M, Hirsch J, Heymsfield S, Gallagher D, Chu F, Leibel R . Effects of gender, body composition, and menopause on plasma concentrations of leptin J Clin Endocrinol Metab 1996 81: 3424–3427.

    CAS  PubMed  Google Scholar 

  3. Leibel R . And finally, genes for human obesity Nature Genet 1997 16: 218–220.

    Article  CAS  Google Scholar 

  4. Hickey M, Israel R, Gardiner S, Considine R, McCammon M, Tyndall G, Howard J, Marks R, Caro J . Gender differences in serum leptin levels in humans Biochem Mol Med 1996 59: 1–6.

    Article  CAS  Google Scholar 

  5. Hickey M, Houmard J, Considine R, Tyndall G, Midgette J, Gavignan K, Weidner M, McCammon M, Israel R, Caro J . Gender-dependent effects of exercise training on serum leptin levels in humans Am J Physiol 1997 272: E562–566.

    CAS  PubMed  Google Scholar 

  6. Kennedy A, Gettys T, Watson P, Wallace P, Ganaway E, Pan Q, Garvey W . The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin-sensitivity, and energy expenditure J Clin Endocrinol Metab 1997 82: 1293–1300.

    CAS  PubMed  Google Scholar 

  7. Saad M, Damani S, Gingerich R, Riad-Gabriel M, Khan A, Boyadjian R, Jinagouda S, el-Tawil K, Rude R, Kamdar V . Sexual dimorphism in plasma leptin concentration J Clin Endocrinol Metab 1997 82: 579–584.

    CAS  PubMed  Google Scholar 

  8. Montague CT, Prins JB, Sanders L, Digby JE, O'Rahilly S . Depot-and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution Diabetes 1997 46: 342–347.

    Article  CAS  Google Scholar 

  9. Hube F, Lietz U, Igel M, Jenson P, Tornqvist H, Joost H, Hauner H . Differences in leptin mRNA levels between omental and subcutaneous adipose tissue from obese humans Horm Metab Res 1996 28: 690–693.

    Article  CAS  Google Scholar 

  10. Kotani K, Tokunaga K, Fujioka S, Kobatake T, Kena Y, Yoshida S, Shimomura I, Tarui S, Matsuzawa Y . Sexual dimorphism of age-related whole body fat changes in the obese Int J Obes Relat Metab Disord 1994 18: 207–212.

    CAS  PubMed  Google Scholar 

  11. Leenen R, Kooy Kvd, Deurenberg P, Seidell J, Weststrate J, Schouten F, Hautvast J . Visceral fat accumulation in obese subjects: relation to energy expenditure and response to weight loss Am J Physiol 1992 263: E913–919.

    Article  CAS  Google Scholar 

  12. Nagy T, Bower G, Trowbridge C, Dezenberg C, Shewchuk R, Goran M . Effects of gender, ethnicity, body composition, and fat distribution on serum leptin levels in children J Clin Endocrinol Metab 1997 82: 2148–2152.

    CAS  PubMed  Google Scholar 

  13. Horlick M, Rosenbaum M, Nidcolson M, Levine L, Fedun B, Wang J, Pierson R, Leibel R . Effect of puberty on the relationship between circulating leptin and body composition J Clin Endocrinol Metab 2000 85: 2509–2518.

    CAS  PubMed  Google Scholar 

  14. Pietrobelli A, Formica C, Wang Z, Heymsfield S . Dual-energy X-ray absorptiometry body composition model: review of physical concepts Am J Physiol 1996 271: E941–951.

    CAS  PubMed  Google Scholar 

  15. Plourde G . The role of radiologic methods in assessing body composition and related metabolic parameters Nutr Rev 1997 55: 289–296.

    Article  CAS  Google Scholar 

  16. Barnard M, Schwieso J, Thomas E, Bell JD, Saeed N, Frost G, Bloom S, Hajnal J . Development of a rapid and efficient magnetic resonance imaging technique for analysis of body fat distribution NMR Biomed 1996 9: 156–164.

    Article  CAS  Google Scholar 

  17. Ross R . Magnetic resonance imaging provides new insights into the characterization of adipose and lean tissue distribution Can J Clin Pharmac 1996 74: 778–785.

    CAS  Google Scholar 

  18. Herbert V, Lau KW, Gottleib CW, Bleicher SJ . Radioimmunoassay determination of insulin concentrations J Clin Endocrinol Metab 1965 2: 1375–1384.

    Article  Google Scholar 

  19. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S et al. Leptin levels in human and rodents: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects Nature Med 1995 1: 1155–1161.

    Article  CAS  Google Scholar 

  20. Statsoft . Statistica, Release 5, '97 Edition Statsoft: Tulsa, OK 1997.

    Google Scholar 

  21. Kolaczynski J, Nyce M, Considine R, Boden G, Nolan J, Henry R, Mudaliar S, Olefsky J, Caro J . Acute and chronic effects of insulin on leptin production in humans: studies in vitro and in vivo Diabetes 1996 45: 699–701.

    Article  CAS  Google Scholar 

  22. Russell C, Petersen R, Rao S, Ricci M, Prasad A, Zhang Y, Brolin R, Fried S . Leptin expression in adipose tissue from obese humans: depot-specific regulation by insulin and dexamethasone Am J Physiol 1998 275: E507–E515.

    CAS  PubMed  Google Scholar 

  23. Weigle D, Ganter S, Kuijper J, Leonetti D, Boyko E, Fujimoto W . Effect of regional fat distribution and Prader-Willi syndrome on plasma leptin levels J Clin Endocrinol Metab 1997 82: 566–570.

    CAS  PubMed  Google Scholar 

  24. Shimizu H, Shimomura Y, Nakanishi Y, Futawatari T, Ohtani K, Sato M, Mori M . Estrogen increases in vivo leptin production in rats and human subjects J Endocrinol 1997 154: 285–292.

    Article  CAS  Google Scholar 

  25. Jockenhovel F, Blum W, Vogel E, Englaro P, Muller-Wieland D, Reinwein D, Rascher W, Krone W . Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men J Clin Endocrinol Metab 1997 82: 2510–2513.

    Article  CAS  Google Scholar 

  26. Wabitsch M, Blum W, Muche R, Braun M, Hube F, Rascher W, Heinze E, Teller W, Hauner H . Contribution of androgens to the gender difference in leptin production in obese children and adolescents J Clin Invest 1997 100: 808–813.

    Article  CAS  Google Scholar 

  27. Haffner S, Miettinen H, Karhapaa P, Mykkanen L, Laasko M . Leptin concentrations, sex hormones, and cortisol in nondiabetic men J Clin Endocrinol Metab 1997 82: 1807–1809.

    CAS  PubMed  Google Scholar 

  28. Harmelen VV, Reynisdottir S, Eriksson P, Thorne A, Hoffstedt J, Lonnqvist F, Arner P . Leptin secretion from subcutaneous and visceral adipose tissue in women Diabetes 1998 47: 913–917.

    Article  Google Scholar 

  29. Peiris AN, Sothmann MS, Hennes MI, Lee MB, Wilson CR, Gustafson AB, Kissebah AH . Relative contribution of obesity and body fat distribution to alternations in glucose insulin homeostasis: predictive values of selected indices in premenopausal women Am J Clin Nutr 1989 49: 758–764.

    Article  CAS  Google Scholar 

  30. Casimirri F, Pasquali R, Cesari M, Melchionda N, Barbara L . Interrelationships between body weight, body fat distribution and insulin in obese women before and after hypocaloric feeding and weight loss Ann Nutr Metab 1989 33: 79–87.

    Article  CAS  Google Scholar 

  31. Barzilai N, She L, Liu B, Vuguin P, Cohen P, Wang J, Rossetti L . Surgical removal of visceral fat reverses hepatic insulin resistance Diabetes 1999 48: 94–98.

    Article  CAS  Google Scholar 

  32. Licinio J, Negrao A, Mantzoros C, Kaklamani V, Wong M, Bongiorno P, Negro P, Mulla A, Veldhuis J, Cearnal L, Flier JS, Gold PW . Sex differences in circulating human leptin pulse amplitude: clinical implications J Clin Endocrinol Metab 1998 83: 4140–4147.

    CAS  PubMed  Google Scholar 

  33. Saad M, Riad-Gabriel M, Khan A, Sharma A, Michael R, Jinagouda S, Boyadjian R, Steil G . Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity J Clin Endocrinol Metab 1998 83: 453–459.

    CAS  PubMed  Google Scholar 

  34. Rosenbaum M, Gertner J . Metabolic clearance rates of synthetic human growth hormone in children, adult women and adult men J Clin Endocrinol Metab 1989 69: 820–824.

    CAS  PubMed  Google Scholar 

  35. Matsuda J, Yokota I, Iida M, Murakami T, Naito E, Ito M, Shima K, Kuroda Y . Serum leptin concentrations in cord blood: relationship to birthweight and gender J Clin Endocrinol Metab 1997 82: 1642–1644.

    Article  CAS  Google Scholar 

  36. Troen P, Oshima H . The testis. In: Felig P, Baxter J, Broadus A, Frohman L (eds). Endocrinology and metabolism McGraw Hill: New York 1981 627–668.

    Google Scholar 

  37. Speroff L . The Ovary. In: Felig P, Baxter J, Broadus A, Frohman L (eds). Endocrinology and metabolism McGraw Hill: New York 1981 669–724.

    Google Scholar 

  38. Ellis K, Nicolson M . Leptin levels and body fatness in children: effects of gender, ethnicity, and sexual development Pediatr Res 1997 42: 484–488.

    Article  CAS  Google Scholar 

  39. Argente J, Barrios V, Chowen J, Sinha M, Considine R . Leptin levels in healthy Spanish children and adolescents, children with obesity, and adolescents with anorexia nervosa and bulimia nervosa J Pediatr 1997 131: 833–838.

    Article  CAS  Google Scholar 

  40. Doucet E, St-Pierre S, Almeras N, Mauriege P, Despres JP, Richard D, Bouchard C, Tremblay A . Fasting insulin levels influence plasma leptin levels independently from the contribution of adiposity: evidence from both a cross-sectional and an intervention study J Clin Endocrinol Metab 2000 85: 4231–4237.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

These studies were supported in part by NIH grants DK30583, DK26687, DK01983, GCRC RR-00047 and GCRC RR00102.

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Authors and Affiliations

  1. Division of Molecular Genetics, Columbia University College of Physicians and Surgeons, New York, USA

    M Rosenbaum & RL Leibel

  2. Department of Medicine, Obesity Research Center, St Luke's-Roosevelt Hospital Center, New York, USA

    A Pietrobelli, JR Vasselli & SB Heymsfield

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  1. M Rosenbaum
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  2. A Pietrobelli
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  4. SB Heymsfield
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Correspondence to M Rosenbaum.

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Rosenbaum, M., Pietrobelli, A., Vasselli, J. et al. Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution. Int J Obes 25, 1365–1371 (2001). https://doi.org/10.1038/sj.ijo.0801730

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