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Circulating sex hormones and gene expression of subcutaneous adipose tissue oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for fat distribution

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Authors:
  • Andersen, Ove ;
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    unknown
  • Pedersen, Steen B ;
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    Orcid logo0000-0002-7838-8063
    Department of Clinical Medicine - The Department of Endocrinology and Metabolism C, Department of Clinical Medicine, Health, Aarhus University
  • Svenstrup, Birgit ;
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    unknown
  • Hansen, Birgitte R ;
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    unknown
  • Paulsen, Søren K ;
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    The Department of Endocrinology and Metabolism C, Faculty of Health Sciences, Aarhus University, Aarhus University
  • Rathje, Gulla S ;
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    unknown
  • Richelsen, Bjørn ;
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    Department of Clinical Medicine - The Department of Endocrinology and Metabolism C, Department of Clinical Medicine, Health, Aarhus University
  • Nielsen, Jens Ole ;
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    unknown
  • Madsbad, Sten ;
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    unknown
  • Iversen, Johan ;
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    unknown
  • Haugaard, Steen B
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    unknown
DOI:
10.1111/j.1365-2265.2007.02872.x
Abstract:
OBJECTIVE: Circulating oestradiol and testosterone, which have been shown to increase in human immunodeficiency virus (HIV)-infected patients following highly active antiretroviral therapy (HAART), may influence fat distribution and insulin sensitivity. Oestradiol increases subcutaneous adipose tissue in humans possibly through binding to oestrogen-receptor-alpha, which in turn activates anti-lipolytic alpha2A-adrenergic-receptor. DESIGN AND METHODS: To address these issues circulating pituitary-gonadal-axis hormones and gene expression of receptors in subcutaneous adipose tissue were determined in 31 nondiabetic HIV-infected male patients receiving HAART (16 with lipodystrophy), in whom measures of fat distribution (CT and DEXA-scans) and insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were available. RESULTS: Total and free oestradiol and testosterone were decreased in lipodystrophic patients compared to nonlipodystrophic patients, whereas luteinizing hormone, follicle-stimulating hormone and prolactin were similar and normal in both study groups. Ratio of subcutaneous to total abdominal fat mass, limb fat, and insulin sensitivity, which were all decreased in lipodystrophic patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression of alpha2A-adrenergic-receptor correlated positively with expression of oestrogen-receptor-alpha. CONCLUSIONS: The results fit the hypothesis that sex hormones play a role in altered fat distribution and insulin sensitivity of male patients with HIV-lipodystrophy. The effect of oestradiol on the subcutaneous fat depot and lipolysis may be mediated in part through binding to the oestrogen-receptor-alpha, in turn activating anti-lipolytic alpha2A-adrenergic-receptor. Udgivelsesdato: 2007-Aug
Type:
Journal article
Language:
English
Published in:
Clinical Endocrinology, 2007, Vol 67, Issue 2, p. 250-8
Keywords:
Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Aromatase; Body Composition; Cross-Sectional Studies; Dehydroepiandrosterone Sulfate; Estradiol; Estrogen Receptor alpha; Gene Expression; Glycerol; Gonadal Steroid Hormones; HIV-1; HIV-Associated Lipodystrophy Syndrome; Humans; Hydrocortisone; Hypoglycemic Agents; Insulin; Linear Models; Lipolysis; Male; Receptors, Adrenergic, alpha-2; Sex Hormone-Binding Globulin; Subcutaneous Fat; Testosterone; Journal Article; Research Support, Non-U.S. Gov't
Main Research Area:
Medical science
Publication Status:
Published
Review type:
Peer Review
Submission year:
2007
Scientific Level:
Scientific
ID:
33844225

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