Does central obesity reflect “Cushing's disease of the omentum”?
IJ Bujalska, S Kumar, PM Stewart - The Lancet, 1997 - thelancet.com
IJ Bujalska, S Kumar, PM Stewart
The Lancet, 1997•thelancet.comBackground Central obesity results in a cluster of metabolic abnormalities contributing to
premature death. Glucocorticoids regulate adipose-tissue differentiation, function, and
distribution, and in excess, cause central obesity. Glucocorticoid hormone action is, in part,
controlled by two isoforms of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD)
which interconverts hormonally active cortisol to inactive cortisone. We studied cortisol
metabolism within different adipose tissue depots. Methods We analysed expression and …
premature death. Glucocorticoids regulate adipose-tissue differentiation, function, and
distribution, and in excess, cause central obesity. Glucocorticoid hormone action is, in part,
controlled by two isoforms of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD)
which interconverts hormonally active cortisol to inactive cortisone. We studied cortisol
metabolism within different adipose tissue depots. Methods We analysed expression and …
Background
Central obesity results in a cluster of metabolic abnormalities contributing to premature death. Glucocorticoids regulate adipose-tissue differentiation, function, and distribution, and in excess, cause central obesity. Glucocorticoid hormone action is, in part, controlled by two isoforms of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) which interconverts hormonally active cortisol to inactive cortisone. We studied cortisol metabolism within different adipose tissue depots.
Methods
We analysed expression and activity of the two isoforms (1 and 2) of 11β-HSD in cultured omental and subcutaneous adipose stromal cells from 16 patients undergoing elective abdominal surgery.
Findings
Only the type 1 isoform (11β-HSD1) was expressed in adipose stromal cells. The predominant activity was oxo-reductase (conversion of cortisone to cortisol greater than cortisol to cortisone) and was higher in omental than subcutaneous fat (cortisone to cortisol, median 57·6 pmol mg−1 h−1 [95% Cl 25·8–112·9] vs 0 pmol mg−1 h−1 [0–0·6], pp<·001). 11β-HSD1 oxo-reductase activity was further increased (127·5 pmol mg−1 h−1 [82·1–209], pp<·05) when omental adipose stromal cells were treated with cortisol and insulin.
Interpretation
Adipose stromal cells from omental fat, but not subcutaneous fat, can generate active cortisol from inactive cortisone through the expression of 11β-HSD1. The expression of this enzyme is increased further after exposure to cortisol and insulin. In vivo, such a mechanism would ensure a constant exposure of glucocorticoid specifically to omental adipose tissue, suggesting that central obesity may reflect "Cushing's disease of the omentum".
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