Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity.
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 11beta-hydroxysteroid dehydrogenase type 1 (11beta-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.


METHODS
A cross-sectional study.


METHODS
Forty-five healthy men and women with body mass index (BMI) 21-36 kg/m(2).


METHODS
In subcutaneous adipose biopsies we measured mRNAs for enzymes metabolizing local oestrogens (aromatase) and androgens [5alpha-reductase type 1; AKR1C2 (3alpha-HSD3); AKR1C3 (17beta-HSD5, 3alpha-HSD2)] and for sex steroid receptors [oestrogen receptor (ER)-alpha 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). 5alpha-Reductase type 1, ER and AR mRNA levels did not predict fat amount or its distribution.


CONCLUSIONS
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.
Wake
Deborah J
DJ
Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Scotland, UK.
Strand
Magnus
M
Rask
Eva
E
Westerbacka
Jukka
J
Livingstone
Dawn E W
DE
Soderberg
Stefan
S
Andrew
Ruth
R
Yki-Jarvinen
Hannele
H
Olsson
Tommy
T
Walker
Brian R
BR
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000328:Adult; D000368:Aged; D000074425:Aldo-Keto Reductase Family 1 Member C3; D001141:Aromatase / Q000235:genetics*; D001706:Biopsy; D050218:Body Fat Distribution; D003430:Cross-Sectional Studies; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010991:Plethysmography; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000235:genetics; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D050507:Subcutaneous Fat, Abdominal / Q000201:enzymology*; D049629:Waist-Hip Ratio; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D015096:3-Hydroxysteroid Dehydrogenases; D000074425:Aldo-Keto Reductase Family 1 Member C3; D001141:Aromatase; D047628:Estrogen Receptor alpha; D012739:Gonadal Steroid Hormones; D006911:Hydroxyprostaglandin Dehydrogenases; D006913:Hydroxysteroid Dehydrogenases; D012333:RNA, Messenger; D011944:Receptors, Androgen; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); C487341:AKR1C3 protein, human