Glucocorticoids and 11beta-hydroxysteroid dehydrogenase in adipose tissue.
The highly prevalent metabolic syndrome (insulin resistance, type 2 diabetes, dyslipidemia, hypertension, along with abdominal obesity) resembles Cushing's syndrome. However, in simple obesity, plasma cortisol levels are not elevated. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), at least in mature adipocytes and hepatocytes, converts inactive circulating 11-keto steroids into active glucocorticoids, amplifying local glucocorticoid action. 11beta-HSD1 is elevated in adipose tissue in obese humans and rodents, suggesting that adipose tissue glucocorticoid excess may explain the conundrum. Indeed, transgenic mice overexpressing 11beta-HSD1 in adipose tissue faithfully replicate the metabolic syndrome. Conversely, 11beta-HSD1(-/-) mice resist the metabolic consequences of stress and high-fat feeding via insulin sensitisation and other advantageous effects in the liver and adipose tissue. Adipose 11beta-HSD1 deficiency contributes to a protective metabolic phenotype, supporting its role as a therapeutic target for the metabolic syndrome.
Seckl
Jonathan R
JR
Endocrinology Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, United Kingdom.
Morton
Nik M
NM
Chapman
Karen E
KE
Walker
Brian R
BR
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology*; D000311:Adrenal Glands / Q000503:physiopathology; D000818:Animals; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology; D008099:Liver / Q000201:enzymology; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009765:Obesity / Q000503:physiopathology; D010902:Pituitary Gland / Q000503:physiopathology
D005938:Glucocorticoids; D042842:11-beta-Hydroxysteroid Dehydrogenases