Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity

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Abstract

Objective

Causes of visceral fat accumulation include glucocorticoid excess or decreased oestrogen/androgen ratio either in plasma or within adipose tissue. In obese subjects, the intra-adipose cortisol-generating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is increased, but information on sex steroid signalling is sparse. We aimed to test associations between body fat or fat distribution and mRNA transcript levels for androgen and oestrogen receptors and for enzymes metabolizing sex steroids in adipose tissue.

Design

A cross-sectional study.

Patients

Forty-five healthy men and women with body mass index (BMI) 21–36 kg/m2.

Measurements

In subcutaneous adipose biopsies we measured mRNAs for enzymes metabolizing local oestrogens (aromatase) and androgens [5α-reductase type 1; AKR1C2 (3α-HSD3); AKR1C3 (17β-HSD5, 3α-HSD2)] and for sex steroid receptors [oestrogen receptor (ER)-α and androgen receptor (AR)]. We related these to body fat mass and distribution.

Results

Generalized obesity (BMI) was associated with increased aromatase mRNA (r = 0·35, P < 0·05). Central obesity (waist: hip ratio) was associated with mRNA for AKR1C2 (r = 0·28, P < 0·05) and AKR1C3 (r = 0·38, P < 0·01) but not aromatase (r = 0·06). 5α-Reductase type 1, ER and AR mRNA levels did not predict fat amount or its distribution.

Conclusion

These data on transcript levels suggest that, in idiopathic obesity, increased intra-adipose oestrogen generation by aromatase predicts peripheral fat distribution, while androgen metabolism by AKR1C isoforms predicts central fat distribution, supporting the hypothesis that intra-adipose sex steroid metabolism is a determinant of gynoid vs. android patterns of body fat.

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