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11β-Hydroxysteroid Dehydrogenase Type 1 and Obesity

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Energy Metabolism and Obesity

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

Individuals with central obesity and the metabolic syndrome appear phenotypically similar to those with Cushing syndrome, a disease of primary glucocorticoid excess. Although morning plasma cortisol concentrations are low or normal in obesity, it is possible that tissue cortisol levels are increased. The enzyme 11α-hydroxysteroid dehydrogenase type 1 (11α-HSD1) catalyzes the conversion of inactive cortisone to active cortisol and is present in many tissues including liver and adipose tissue. Transgenic mice overexpressing 11α-HSD1 selectively in adipose tissue develop central obesity with all the features of the metabolic syndrome. In humans, tissue-specific dysregulation of glucocorticoids occurs in simple obesity, with increased 11α-HSD1 activity in subcutaneous adipose tissue and decreased activity in the liver. 11α-HSD1 is highly regulated, and altered plasticity may predispose to metabolic disease. Genetic studies have shown associations between polymorphisms in the HSD11B1 gene and components of the metabolic syndrome. Nonspecific inhibition of this enzyme leads to improved hepatic insulin sensitivity, while more selective compounds are being developed to potentially treat central obesity and the associated metabolic complications.

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Abstract

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Authors
  1. Roland H. Stimson
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  2. Brian R. Walker
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  1. University of lowa, lowa City, IA

    Patricia A. Donohoue MD

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Stimson, R.H., Walker, B.R. (2007). 11β-Hydroxysteroid Dehydrogenase Type 1 and Obesity. In: Donohoue, P.A. (eds) Energy Metabolism and Obesity. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-60327-139-4_10

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  • DOI: https://doi.org/10.1007/978-1-60327-139-4_10

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