HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) All Versions of this Article: JOE-09-0003v1 201/2/211    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Livingstone, D. Articles by Andrew, R. Search for Related Content PubMed PubMed Citation Articles by Livingstone, D. Articles by Andrew, R.

D Livingstone, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
S Grassick, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
G Currie, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
B Walker, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
R Andrew, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

Correspondence: Ruth Andrew, Email: ruth.andrew{at}ed.ac.uk

Abstract

Objective: In obese humans metabolism of glucocorticoids by 11beta-HSD1 and A-ring reduction (by 5alpha- and 5beta-reductases) is dysregulated in a tissue specific manner. These changes have been recapitulated in leptin resistant obese Zucker rats but were not observed in high fat fed Wistar rats. Recent data from mouse models suggest such discrepancies may reflect differences in leptin signalling. We therefore compared glucocorticoid metabolism in murine models of leptin deficiency and resistance.

Methods: Male ob/ob and db/db mice and their respective littermate controls (n=10-12/group) were studied at the age of 12 weeks. Enzyme activities and mRNA expression were quantified in snap-frozen tissues.

Results: The patterns of altered pathways of steroid metabolism in obesity were similar in ob/ob and db/db mice. In liver, 5beta-reductase activity and mRNA were increased and 11beta HSD1 decreased in obese mice, whereas 5alpha-reductase 1 mRNA was not altered. In visceral adipose depots, 5beta reductase was not expressed, 11beta HSD1 activity was increased and 5alpha-reductase 1 mRNA was not altered in obesity. In contrast, in sub-cutaneous adipose tissue 11beta HSD1 and 5alpha-reductase 1 mRNA were decreased.

Conclusion: There were no systematic differences between ob/ob and db/db murine models of obesity suggesting that variations in leptin signalling through the short splice variant of the Ob receptor do not contribute to dysregulation of glucocorticoid metabolism.