Omental 11beta-hydroxysteroid dehydrogenase 1 correlates with fat cell size independently of obesity.
OBJECTIVE
In ideopathic obesity, there is evidence that enhanced cortisol regeneration within abdominal subcutaneous adipose tissue may contribute to adiposity and metabolic disease. Whether the cortisol regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), or glucocorticoid receptor (GRalpha) levels are altered in other adipose depots remains uncertain. Our objective was to determine the association between 11betaHSD1 and GRalpha mRNA levels in four distinct adipose depots and measures of obesity and the metabolic syndrome.


METHODS
Adipose tissue biopsies were collected from subcutaneous (abdominal, thigh, gluteal) and intra-abdominal (omental) adipose depots from 21 women. 11betaHSD1 and GRalpha mRNA levels were measured by real-time polymerase chain reaction. Body composition, fat distribution, fat cell size, and blood lipid, glucose, and insulin levels were measured.


RESULTS
11betaHSD1 mRNA was highest in abdominal subcutaneous (p < 0.001) and omental (p < 0.001) depots and was positively correlated with BMI and visceral adiposity in all depots. Omental 11betaHSD1 correlated with percent body fat (R = 0.462, p < 0.05), fat cell size (R = 0.72, p < 0.001), and plasma triglycerides (R = 0.46, p < 0.05). Conversely, GRalpha mRNA was highest in omental fat (p < 0.001). GRalpha mRNA was negatively correlated with BMI in the abdominal subcutaneous (R = -0.589, p < 0.05) and omental depots (R = -0.627, p < 0.05). Omental GRalpha mRNA was inversely associated with visceral adiposity (R = -0.507, p < 0.05), fat cell size (R = -0.52, p < 0.01), and triglycerides (R = -0.50, p < 0.05).


CONCLUSIONS
Obesity was associated with elevated 11betaHSD1 mRNA in all adipose compartments. GRalpha mRNA is reduced in the omental depot with obesity. The novel correlation of 11betaHSD1 with omental fat cell size, independent of obesity, suggests that intracellular cortisol regeneration is a strong predictor of hypertrophy in the omentum.
Michailidou
Zoi
Z
Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Jensen
Michael D
MD
Dumesic
Daniel A
DA
Chapman
Karen E
KE
Seckl
Jonathan R
JR
Walker
Brian R
BR
Morton
Nicholas M
NM
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology* / Q000473:pathology; D016632:Apolipoprotein A-I / Q000097:blood; D015992:Body Mass Index; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000201:enzymology / Q000473:pathology*; D009852:Omentum / Q000201:enzymology*; D050177:Overweight / Q000502:physiology*; D013030:Spain
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D007328:Insulin; D008055:Lipids; D019314:Dehydroepiandrosterone Sulfate; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1