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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
11beta-hydroxysteroid dehydrogenase type 1 and obesity
Nicholas M Morton1, Jonathan R Seckl
1Endocrinology Unit, Centre for Cardiovascular Sciences, Queens Medical Research Institute, Edinburgh University, Edinburgh, UK.
Frontiers of Hormone Research
|January 31, 2008
Summary
Elevated 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in adipose tissue drives metabolic syndrome. Inhibiting this enzyme shows therapeutic promise for obesity and related conditions.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Molecular Biology
Background:
- Metabolic syndrome shares features with Cushing's syndrome, but with normal or lower plasma cortisol.
- Intracellular glucocorticoid reactivation, particularly in adipose tissue, is implicated in metabolic disease.
- 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) reactivates glucocorticoids locally.
Purpose of the Study:
- To investigate the role of adipose tissue 11beta-HSD1 in metabolic syndrome development.
- To assess the therapeutic potential of 11beta-HSD1 inhibition for metabolic disorders.
Main Methods:
- Generation of transgenic mice with adipose-selective or liver-specific 11beta-HSD1 overexpression.
- Analysis of metabolic parameters in transgenic mice and 11beta-HSD1 gene knock-out mice.
- Evaluation of high-fat diet effects on 11beta-HSD1 expression and metabolic outcomes.
Main Results:
- Adipose-selective 11beta-HSD1 overexpression induced obesity, hyperglycemia, insulin resistance, dyslipidemia, and hypertension.
- Liver-specific overexpression resulted in an attenuated metabolic syndrome without obesity.
- 11beta-HSD1 gene knock-out mice showed improved glucose tolerance, favorable lipid profiles, and reduced weight gain on a high-fat diet.
Conclusions:
- Elevated 11beta-HSD1 in adipose tissue is a key driver of metabolic syndrome.
- Targeting 11beta-HSD1 offers a promising therapeutic strategy for metabolic syndrome, obesity, and cardiovascular disease.
- Endogenous downregulation of 11beta-HSD1 may contribute to obesity resistance.
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