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Central and peripheral glucocorticoid receptor function in abdominal obesity

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Abstract

Abdominal obesity seems to be associated with a moderately deranged feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis where central glucocorticoid receptors (GR) are involved. Therefore, functions of central and peripheral GR were compared in this study. Furthermore, since trinucleotide repeats in early exons of steroid hormone receptor genes influence transcription, and therefore may influence receptor density, this was also studied. Ten middle-aged men, 5 with abdominal obesity and 5 controls, were studied. The suppression of dexamethasone (dex) on serum cortisol was used in dose-response tests to assess the function of central GR. Abdominal adipose tissue biopsies were incubated and exposed to cortisol in different concentrations, and the function of the peripheral GR assayed as induction of lipoprotein lipase (LPL) activity. Aberrant expansion of exonic trinucleotide repeats in the first coding exon of the GR gene was studied by sequencing of genomic DNA. Results showed that men with abdominal obesity showed less inhibition of serum cortisol by dex, particularly at lower concentrations, while in the controls cortisol secretion was inhibited in an apparent dose-response manner. LPL activity in adipose tissue was lower in abdominal obese men than in controls. However, the sensitivity to cortisol was not different between the groups. There was no evidence for expansion of trinucleotide repeats. These results suggest that the central GR and the peripheral GR in adipose tissue exhibit functional differences in abdominal obesity.

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Authors and Affiliations

  1. Department of Heart and Lung Diseases, Sahlgrenska Hospital, University of Göteborg, SE-413 45, Göteborg, Sweden

    T. Ljung & P. Björntorp

  2. Department of Psychiatry, Sahlgrenska Hospital, University of Göteborg, Göteborg, Sweden

    A. C. Ahlberg

  3. Department of Physiology, Sahlgrenska Hospital, University of Göteborg, Göteborg, Sweden

    S. Edén

  4. The Wallenberg Laboratory, Sahlgrenska Hospital, University of Göteborg, Göteborg, Sweden

    M. Ottosson & B. Odén

  5. Department of Medical Nutrition, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden

    S. Okret

  6. Department of Clinical Sciences, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden

    M. Brönnegård & P. Stierna

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  1. T. Ljung
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Correspondence to T. Ljung.

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Ljung, T., Ottosson, M., Ahlberg, A.C. et al. Central and peripheral glucocorticoid receptor function in abdominal obesity. J Endocrinol Invest 25, 229–235 (2002). https://doi.org/10.1007/BF03343995

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