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Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men

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Abstract
Context: Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men. Objective: The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines. Design: Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches. Results: Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1 alpha, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo. Conclusions: Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.
Keywords
ESTROGEN, RISK, DISEASE, CELLS, ESTRADIOL, INSULIN, MIDDLE-AGED MEN, ADIPOSE-TISSUE, CHEMOKINE EXPRESSION, TESTOSTERONE

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MLA
Ruige, Johannes, Marlies Bekaert, Bruno Lapauw, et al. “Sex Steroid-induced Changes in Circulating Monocyte Chemoattractant Protein-1 Levels May Contribute to Metabolic Dysfunction in Obese Men.” JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 97.7 (2012): E1187–E1191. Print.
APA
Ruige, J., Bekaert, M., Lapauw, B., Fiers, T., Lehr, S., Hartwig, S., Herzfeld de Wiza, D., et al. (2012). Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 97(7), E1187–E1191.
Chicago author-date
Ruige, Johannes, Marlies Bekaert, Bruno Lapauw, Tom Fiers, Stefan Lehr, Sonja Hartwig, Daniella Herzfeld de Wiza, et al. 2012. “Sex Steroid-induced Changes in Circulating Monocyte Chemoattractant Protein-1 Levels May Contribute to Metabolic Dysfunction in Obese Men.” Journal of Clinical Endocrinology & Metabolism 97 (7): E1187–E1191.
Chicago author-date (all authors)
Ruige, Johannes, Marlies Bekaert, Bruno Lapauw, Tom Fiers, Stefan Lehr, Sonja Hartwig, Daniella Herzfeld de Wiza, Martina Schiller, Waltraud Passlack, Yves Van Nieuwenhove, Piet Pattyn, Claude Cuvelier, Youri Taes, Henrike Sell, Juergen Eckel, Jean Kaufman, and D Margriet Ouwens. 2012. “Sex Steroid-induced Changes in Circulating Monocyte Chemoattractant Protein-1 Levels May Contribute to Metabolic Dysfunction in Obese Men.” Journal of Clinical Endocrinology & Metabolism 97 (7): E1187–E1191.
Vancouver
1.
Ruige J, Bekaert M, Lapauw B, Fiers T, Lehr S, Hartwig S, et al. Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM. 2012;97(7):E1187–E1191.
IEEE
[1]
J. Ruige et al., “Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men,” JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, vol. 97, no. 7, pp. E1187–E1191, 2012.
@article{3087573,
  abstract     = {Context: Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men. 
Objective: The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines. 
Design: Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches. 
Results: Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1 alpha, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo. 
Conclusions: Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.},
  author       = {Ruige, Johannes and Bekaert, Marlies and Lapauw, Bruno and Fiers, Tom and Lehr, Stefan and Hartwig, Sonja and Herzfeld de Wiza, Daniella and Schiller, Martina and Passlack, Waltraud and Van Nieuwenhove, Yves and Pattyn, Piet and Cuvelier, Claude and Taes, Youri and Sell, Henrike and Eckel, Juergen and Kaufman, Jean and Ouwens, D Margriet},
  issn         = {0021-972X},
  journal      = {JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM},
  keywords     = {ESTROGEN,RISK,DISEASE,CELLS,ESTRADIOL,INSULIN,MIDDLE-AGED MEN,ADIPOSE-TISSUE,CHEMOKINE EXPRESSION,TESTOSTERONE},
  language     = {eng},
  number       = {7},
  pages        = {E1187--E1191},
  title        = {Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men},
  url          = {http://dx.doi.org/10.1210/jc.2011-3069},
  volume       = {97},
  year         = {2012},
}

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