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Sex-specific determinants of serum adiponectin in older adults: the role of endogenous sex hormones

Abstract

Objective:

To assess the sex-specific association of adiponectin with multiple factors thought to influence its levels, with a special emphasis on endogenous sex hormones.

Design and methods:

A cross-sectional study of determinants of serum adiponectin in 873 men and 673 postmenopausal women, ages 50–92. Factors evaluated include age, body size, fat distribution, lifestyle (exercise, smoking, alcohol intake), insulin resistance, renal function and endogenous sex hormone levels (total and bioavailable testosterone and estradiol).

Results:

Median serum adiponectin was 50% higher in women than men (P<0.001). In unadjusted analyses, adiponectin was positively related to age, alcohol intake, high-density lipoprotein (HDL) and testosterone, and negatively related to waist girth, body mass index, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), triglycerides and bioavailable estradiol in both sexes (all P<0.01). Adiponectin was positively related to blood urea nitrogen, a measure of renal function, in men only (P<0.001). Sex-specific multivariate linear regressions adjusting for HDL and triglycerides showed that only age, HOMA-IR and sex hormones independently predicted circulating adiponectin for both men and women. Higher levels of endogenous testosterone and lower bioavailable estradiol concentrations each predicted higher adiponectin; this was true for both sexes, and was not explained by differences in age, adiposity, alcohol intake, insulin resistance or lipoprotein levels.

Conclusions:

The association of adiponectin with the factors studied here is strikingly similar for men and women. Sex differences in circulating adiponectin levels in older adults cannot be explained by sex hormone regulation.

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References

  1. Chandran M, Phillips SA, Ciaraldi T, Henry RR . Adiponectin: more than just another fat cell hormone? Diabetes Care 2003; 26: 2442–2450.

    Article  CAS  PubMed  Google Scholar 

  2. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000; 20: 1595–1599.

    Article  CAS  PubMed  Google Scholar 

  3. Gavrila A, Chan JL, Yiannakouris N, Kontogianni M, Miller LC, Orlova C et al. Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies. J Clin Endocrinol Metab 2003; 88: 4823–4831.

    Article  CAS  PubMed  Google Scholar 

  4. Motoshima H, Wu X, Sinha MK, Hardy VE, Rosato EL, Barbot DJ et al. Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone. J Clin Endocrinol Metab 2002; 87: 5662–5667.

    Article  CAS  PubMed  Google Scholar 

  5. Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 2003; 46: 459–469.

    Article  CAS  PubMed  Google Scholar 

  6. Trujillo ME, Scherer PE . Adiponectin – journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J Intern Med 2005; 257: 167–175.

    Article  CAS  PubMed  Google Scholar 

  7. Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes 2002; 51: 2734–2741.

    Article  CAS  PubMed  Google Scholar 

  8. Yamamoto Y, Hirose H, Saito I, Tomita M, Taniyama M, Matsubara K et al. Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population. Clin Sci (London) 2002; 103: 137–142.

    Article  CAS  Google Scholar 

  9. Sieminska L, Wojciechowska C, Niedziolka D, Marek B, Kos-Kudla B, Kajdaniuk D et al. Effect of postmenopause and hormone replacement therapy on serum adiponectin levels. Metabolism 2005; 54: 1610–1614.

    Article  CAS  PubMed  Google Scholar 

  10. Combs TP, Berg AH, Rajala MW, Klebanov S, Iyengar P, Jimenez-Chillaron JC et al. Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes 2003; 52: 268–276.

    Article  CAS  PubMed  Google Scholar 

  11. Lanfranco F, Zitzmann M, Simoni M, Nieschlag E . Serum adiponectin levels in hypogonadal males: influence of testosterone replacement therapy. Clin Endocrinol (Oxford) 2004; 60: 500–507.

    Article  CAS  Google Scholar 

  12. Page ST, Herbst KL, Amory JK, Coviello AD, Anawalt BD, Matsumoto AM et al. Testosterone administration suppresses adiponectin levels in men. J Androl 2005; 26: 85–92.

    CAS  PubMed  Google Scholar 

  13. Ducluzeau PH, Cousin P, Malvoisin E, Bornet H, Vidal H, Laville M et al. Glucose-to-insulin ratio rather than sex hormone-binding globulin and adiponectin levels is the best predictor of insulin resistance in nonobese women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88: 3626–3631.

    Article  CAS  PubMed  Google Scholar 

  14. Orio Jr F, Palomba S, Cascella T, Milan G, Mioni R, Pagano C et al. Adiponectin levels in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88: 2619–2623.

    Article  CAS  PubMed  Google Scholar 

  15. Spranger J, Mohlig M, Wegewitz U, Ristow M, Pfeiffer AF, Schill T et al. Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndrome. Clin Endocrinol (Oxford) 2004; 61: 738–746.

    Article  CAS  Google Scholar 

  16. Havel PJ . Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 2004; 53 (Suppl 1): S143–S151.

    Article  CAS  PubMed  Google Scholar 

  17. Halleux CM, Takahashi M, Delporte ML, Detry R, Funahashi T, Matsuzawa Y et al. Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue. Biochem Biophys Res Commun 2001; 288: 1102–1107.

    Article  CAS  PubMed  Google Scholar 

  18. Miyazaki T, Shimada K, Mokuno H, Daida H . Adipocyte derived plasma protein, adiponectin, is associated with smoking status in patients with coronary artery disease. Heart 2003; 89: 663.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Thamer C, Haap M, Fritsche A, Haering H, Stumvoll M . Relationship between moderate alcohol consumption and adiponectin and insulin sensitivity in a large heterogeneous population. Diabetes Care 2004; 27: 1240.

    Article  PubMed  Google Scholar 

  20. Hulver MW, Zheng D, Tanner CJ, Houmard JA, Kraus WE, Slentz CA et al. Adiponectin is not altered with exercise training despite enhanced insulin action. Am J Physiol Endocrinol Metab 2002; 283: E861–E865.

    Article  CAS  PubMed  Google Scholar 

  21. Marcell TJ, McAuley KA, Traustadottir T, Reaven PD . Exercise training is not associated with improved levels of C-reactive protein or adiponectin. Metabolism 2005; 54: 533–541.

    Article  CAS  PubMed  Google Scholar 

  22. Sierksma A, Patel H, Ouchi N, Kihara S, Funahashi T, Heine RJ et al. Effect of moderate alcohol consumption on adiponectin, tumor necrosis factor-alpha, and insulin sensitivity. Diabetes Care 2004; 27: 184–189.

    Article  CAS  PubMed  Google Scholar 

  23. The hypertension detection and follow-up program. Hypertension detection and follow-up program cooperative group. Prev Med 1976; 5: 207–215.

  24. Tremblay RR, Dube JY . Plasma concentrations of free and non-TeBG bound testosterone in women on oral contraceptives. Contraception 1974; 10: 599–605.

    Article  CAS  PubMed  Google Scholar 

  25. Friedwald W, Levy R, Frederickson D . Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

    Google Scholar 

  26. Desbuquois B, Aurbach GD . Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. J Clin Endocrinol Metab 1971; 33: 732–738.

    Article  CAS  PubMed  Google Scholar 

  27. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  PubMed  Google Scholar 

  28. Rose G, McCartney P, Reid DD . Self-administration of a questionnaire on chest pain and intermittent claudication. Br J Prev Soc Med 1977; 31: 42–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Report of a WHO Consultation. Part 1: Diagnosis and Classification of Diabetes Mellitus. World Health Organization: Geneva, 1999.

  30. Kirschner MA, Samojlik E . Sex hormone metabolism in upper and lower body obesity. Int J Obes 1991; 15 (Suppl 2): 101–108.

    CAS  PubMed  Google Scholar 

  31. Kirschner MA, Samojlik E, Drejka M, Szmal E, Schneider G, Ertel N . Androgen–estrogen metabolism in women with upper body versus lower body obesity. J Clin Endocrinol Metab 1990; 70: 473–479.

    Article  CAS  PubMed  Google Scholar 

  32. Kalish GM, Barrett-Connor E, Laughlin GA, Gulanski BI . Association of endogenous sex hormones and insulin resistance among postmenopausal women: results from the Postmenopausal Estrogen/Progestin Intervention Trial. J Clin Endocrinol Metab 2003; 88: 1646–1652.

    Article  CAS  PubMed  Google Scholar 

  33. Isobe T, Saitoh S, Takagi S, Takeuchi H, Chiba Y, Katoh N et al. Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study. Eur J Endocrinol 2005; 153: 91–98.

    Article  CAS  PubMed  Google Scholar 

  34. Tanko LB, Bruun JM, Alexandersen P, Bagger YZ, Richelsen B, Christiansen C et al. Novel associations between bioavailable estradiol and adipokines in elderly women with different phenotypes of obesity: implications for atherogenesis. Circulation 2004; 110: 2246–2252.

    Article  CAS  PubMed  Google Scholar 

  35. Kwon K, Jung SH, Choi C, Park SH . Reciprocal association between visceral obesity and adiponectin: in healthy premenopausal women. Int J Cardiol 2005; 101: 385–390.

    Article  PubMed  Google Scholar 

  36. Couillard CGJ, Bergeron J, Leon AS, Rao DC, Skinner JS, Wilmore JH et al. Contribution of body fatness and adipose tissue distribution to the age variation in plasma steroid hormone concentrations in men: the HERITAGE Family Study. J Clin Endocrinol Metab 2000; 85: 1026–1031.

    CAS  PubMed  Google Scholar 

  37. Seidell JC, Bjorntorp P, Sjostrom L, Kvist H, Sannerstedt R . Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels. Metabolism 1990; 39: 897–901.

    Article  CAS  PubMed  Google Scholar 

  38. Arner P . Effects of testosterone on fat cell lipolysis. Species differences and possible role in polycystic ovarian syndrome. Biochimie 2005; 87: 39–43.

    Article  CAS  PubMed  Google Scholar 

  39. Oh JY, Barrett-Connor E, Wedick NM, Wingard DL . Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care 2002; 25: 55–60.

    Article  CAS  PubMed  Google Scholar 

  40. Steffes MW, Gross MD, Schreiner PJ, Yu X, Hilner JE, Gingerich R et al. Serum adiponectin in young adults – interactions with central adiposity, circulating levels of glucose, and insulin resistance: the CARDIA study. Ann Epidemiol 2004; 14: 492–498.

    Article  PubMed  Google Scholar 

  41. Bottner A, Kratzsch J, Muller G, Kapellen TM, Bluher S, Keller E et al. Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab 2004; 89: 4053–4061.

    Article  PubMed  Google Scholar 

  42. Choi KM, Lee J, Lee KW, Seo JA, Oh JH, Kim SG et al. The associations between plasma adiponectin, ghrelin levels and cardiovascular risk factors. Eur J Endocrinol 2004; 150: 715–718.

    Article  CAS  PubMed  Google Scholar 

  43. Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J 2004; 68: 975–981.

    Article  CAS  PubMed  Google Scholar 

  44. Ryan AS, Berman DM, Nicklas BJ, Sinha M, Gingerich RL, Meneilly GS et al. Plasma adiponectin and leptin levels, body composition, and glucose utilization in adult women with wide ranges of age and obesity. Diabetes Care 2003; 26: 2383–2388.

    Article  CAS  PubMed  Google Scholar 

  45. Matsubara M, Maruoka S, Katayose S . Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 2002; 87: 2764–2769.

    Article  CAS  PubMed  Google Scholar 

  46. Adamczak M, Rzepka E, Chudek J, Wiecek A . Ageing and plasma adiponectin concentration in apparently healthy males and females. Clin Endocrinol (Oxford) 2005; 62: 114–118.

    Article  CAS  Google Scholar 

  47. Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R . Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2002; 290: 1084–1089.

    Article  CAS  PubMed  Google Scholar 

  48. Hoffstedt J, Arvidsson E, Sjolin E, Wahlen K, Arner P . Adipose tissue adiponectin production and adiponectin serum concentration in human obesity and insulin resistance. J Clin Endocrinol Metab 2004; 89: 1391–1396.

    Article  CAS  PubMed  Google Scholar 

  49. Pischon T, Girman CJ, Rifai N, Hotamisligil GS, Rimm EB . Association between dietary factors and plasma adiponectin concentrations in men. Am J Clin Nutr 2005; 81: 780–786.

    Article  CAS  PubMed  Google Scholar 

  50. Gavrila A, Peng CK, Chan JL, Mietus JE, Goldberger AL, Mantzoros CS . Diurnal and ultradian dynamics of serum adiponectin in healthy men: comparison with leptin, circulating soluble leptin receptor, and cortisol patterns. J Clin Endocrinol Metab 2003; 88: 2838–2843.

    Article  CAS  PubMed  Google Scholar 

  51. Shea SA, Hilton MF, Orlova C, Ayers RT, Mantzoros CS . Independent circadian and sleep/wake regulation of adipokines and glucose in humans. J Clin Endocrinol Metab 2005; 90: 2537–2544.

    Article  CAS  PubMed  Google Scholar 

  52. Yildiz BO, Suchard MA, Wong ML, McCann SM, Licinio J . Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity. Proc Natl Acad Sci USA 2004; 101: 10434–10439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Pischon T, Hotamisligil G, Rimm E . Adiponectin: stability in plasma over 36 hours and within-person variation over 1 year. Clin Chem 2003; 49: 650–652.

    Article  CAS  PubMed  Google Scholar 

  54. Xu A, Chan KW, Hoo RL, Wang Y, Tan KC, Zhang J et al. Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J Biol Chem 2005; 280: 18073–18080.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

GA Laughlin was supported by American Heart Association Award 0315024Y. The Rancho Bernardo Study was funded by research Grant AG07181 from the National Institute on Aging and Grant DK31801 from the National Institute of Diabetes and Digestive and Kidney Diseases.

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Correspondence to G A Laughlin.

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Laughlin, G., Barrett-Connor, E. & May, S. Sex-specific determinants of serum adiponectin in older adults: the role of endogenous sex hormones. Int J Obes 31, 457–465 (2007). https://doi.org/10.1038/sj.ijo.0803427

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  • DOI: https://doi.org/10.1038/sj.ijo.0803427

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