The Functional Consequences of 11β-Hydroxysteroid Dehydrogenase Expression in Adipose Tissue

Abstract

Clinical observations have highlighted the link between glucocorticoids and obesity. While exogenous glucocorticoids in excess predispose to the development of central obesity, we have focused on cortisol metabolism within human adipose tissue. 11β-hydroxysteroid dehydrogenase (11β-HSD) inter-converts the active glucocorticoid, cortisol, and inactive cortisone. 11β-HSD1, the only isoform expressed in adipose tissue, acts predominantly as an oxoreductase to generate cortisol. Expression is higher in omental compared to subcutaneous preadipocytes and activity and expression are potently regulated by growth factors and cytokines. Mice over-expressing 11β-HSD1 specifically within adipocytes develop central obesity. However, the situation is less clear in humans. Globally, there appears to be inhibition of the enzyme, but expression in human obesity is still not fully characterized; its functional role in adipocyte biology remains to be elucidated. In vitro, 11β-HSD1 appears to function in promoting adipocyte differentiation and limiting preadipocyte proliferation, but the impact of these effects in vivo upon the regulation of fat mass remains to be defined. Clinical studies utilizing selective 11β-HSD1 inhibitors may help to answer this question.

11β-Hydroxysteroid Dehydrogenase - Obesity - Adipose Tissue - Proliferation - Differentiation - Cortisol - Preadipocyte

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