title: Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 1α, 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.
authors.affiliation: Department of Endocrinology, Ghent University Hospital, 9000 Ghent, Belgium.
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Ruige
authors.forename: Marlies
authors.initials: M
authors.lastname: Bekaert
authors.forename: Bruno
authors.initials: B
authors.lastname: Lapauw
authors.forename: Tom
authors.initials: T
authors.lastname: Fiers
authors.forename: Stefan
authors.initials: S
authors.lastname: Lehr
authors.forename: Sonja
authors.initials: S
authors.lastname: Hartwig
authors.forename: Daniella
authors.initials: D
authors.lastname: Herzfeld de Wiza
authors.forename: Martina
authors.initials: M
authors.lastname: Schiller
authors.forename: Waltraud
authors.initials: W
authors.lastname: Passlack
authors.forename: Yves
authors.initials: Y
authors.lastname: Van Nieuwenhove
authors.forename: Piet
authors.initials: P
authors.lastname: Pattyn
authors.forename: Claude
authors.initials: C
authors.lastname: Cuvelier
authors.forename: Youri E
authors.initials: YE
authors.lastname: Taes
authors.forename: Henrike
authors.initials: H
authors.lastname: Sell
authors.forename: Juergen
authors.initials: J
authors.lastname: Eckel
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Kaufman
authors.forename: D Margriet
authors.initials: DM
authors.lastname: Ouwens
mesh_terms: D054392:Adipokines / Q000097:blood / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood* / Q000502:physiology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D012739:Gonadal Steroid Hormones / Q000097:blood* / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
chemical_list: D054392:Adipokines; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D012739:Gonadal Steroid Hormones