Down-regulation of adipose 11beta-hydroxysteroid dehydrogenase type 1 by high-fat feeding in mice: a potential adaptive mechanism counteracting metabolic disease.

• Abstract: The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) amplifies intracellular glucocorticoid action in vivo. 11beta-HSD-1 activity is increased in adipose tissues of obese humans and genetically obese rodents, providing a mechanistic basis for the similarities between metabolic disease arising from high circulating glucocorticoids (Cushing's syndrome) and idiopathic obesity/metabolic syndrome where plasma glucocorticoids are typically unaltered. Fat-specific overexpression of 11beta-HSD-1 produces a metabolic syndrome in mice, whereas 11beta-HSD-1 null mice resist high-fat diet (HF)-induced visceral obesity and its metabolic consequences. Here we compared the effects of chronic (18 wk) HF feeding on adipose 11beta-HSD-1 activity in strains of mice that are either resistant (A/J) or prone (C57BL/6J) to metabolic disease. 11beta-HSD-1 activity was highest in sc fat, followed by epididymal fat, with lowest activity in the mesenteric visceral depot of both strains. 11beta-HSD-1 activity was lower in white adipose tissues of A/J compared with C57BL/6J mice. Chronic HF feeding unexpectedly caused a down-regulation of 11beta-HSD-1 in adipose tissues of both strains, despite comparable adiposity. However, A/J mice down-regulated adipose 11beta-HSD-1 to a significantly lower level than C57BL/6J mice in white and thermogenic brown adipose tissues. We propose that a lower adipose 11beta-HSD-1 set point affords a metabolic protection to A/J mice. Adaptive down-regulation of adipose 11beta-HSD-1 in response to chronic HF represents a novel mechanism that may counteract metabolic disease.
• Authors: Nicholas M Morton, Lynne Ramage, Jonathan R Seckl (Affiliation: Endocrinology Unit, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, Scotland, United Kingdom. nik.morton at ed.ac.uk)
• Journal: Endocrinology (Endocrinology) Vol. 145 Issue 6 Pg. 2707-12 (Jun 2004) ISSN: 0013-7227 [Print] United States
• PMID: 15044372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• 11-beta-Hydroxysteroid Dehydrogenase Type 1

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 1 (metabolism)
• Adaptation, Physiological
• Adipose Tissue (enzymology)
• Animals
• Dietary Fats (administration & dosage)
• Down-Regulation
• Epididymis
• Male
• Mesentery
• Metabolic Diseases (physiopathology)
• Mice
• Mice, Inbred C57BL
• Subcutaneous Tissue
• Tissue Distribution
• Viscera