Obesity and corticosteroids: 11beta-hydroxysteroid type 1 as a cause and therapeutic target in metabolic disease

Mol Cell Endocrinol. 2010 Mar 25;316(2):154-64. doi: 10.1016/j.mce.2009.09.024. Epub 2009 Oct 3.


The metabolic abnormalities found associated with high blood glucocorticoid levels (e.g. rare Cushing's syndrome) include insulin-resistance, visceral obesity, hypertension, dyslipidaemia and an increased risk of cardiovascular diseases. The same constellation of abnormalities is found in the highly prevalent idiopathic obesity/insulin-resistance (metabolic)-syndrome. It is now apparent that tissue-specific changes in cortisol metabolism explain these parallels rather than altered blood cortisol levels. Primary among these changes is increased intracellular glucocorticoid reactivation, catalysed by the enzyme 11beta-hydroxysteroid dehydrogenase type (HSD)-1 in obese adipose tissue. Liver, skeletal muscle, endocrine pancreas, blood vessels and leukocytes express 11beta-HSD1 and their potential role in metabolic disease is discussed. The weight of evidence, much of it gained from animal models, suggests that therapeutic inhibition of 11beta-HSD1 will be beneficial in most cellular contexts, with clinical trials supportive of this concept.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism*
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Adipose Tissue / physiopathology
  • Adrenal Cortex Hormones / metabolism*
  • Animals
  • Cushing Syndrome / metabolism
  • Cushing Syndrome / physiopathology
  • Glucocorticoids / metabolism
  • Glucocorticoids / pharmacology
  • Humans
  • Hydrocortisone / metabolism*
  • Metabolic Syndrome* / drug therapy
  • Metabolic Syndrome* / enzymology
  • Metabolic Syndrome* / physiopathology
  • Obesity* / drug therapy
  • Obesity* / enzymology
  • Obesity* / physiopathology
  • Tissue Distribution


  • Adrenal Cortex Hormones
  • Glucocorticoids
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Hydrocortisone