Change search
ReferencesLink to record
Permanent link

Direct link
Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Show others and affiliations
2009 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 58, no 1, 46-53 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates cortisol from cortisone. 11beta-HSD1 mRNA and activity are increased in vitro in subcutaneous adipose tissue from obese patients. Inhibition of 11beta-HSD1 is a promising therapeutic approach in type 2 diabetes. However, release of cortisol by 11beta-HSD1 from adipose tissue and its effect on portal vein cortisol concentrations have not been quantified in vivo.

RESEARCH DESIGN AND METHODS: Six healthy men underwent 9,11,12,12-[(2)H](4)-cortisol infusions with simultaneous sampling of arterialized and superficial epigastric vein blood sampling. Four men with stable chronic liver disease and a transjugular intrahepatic porto-systemic shunt in situ underwent tracer infusion with simultaneous sampling from the portal vein, hepatic vein, and an arterialized peripheral vein.

RESULTS: Significant cortisol and 9,12,12-[(2)H](3)-cortisol release were observed from subcutaneous adipose tissue (15.0 [95% CI 0.4-29.5] and 8.7 [0.2-17.2] pmol . min(-1) . 100 g(-1) adipose tissue, respectively). Splanchnic release of cortisol and 9,12,12-[(2)H](3)-cortisol (13.5 [3.6-23.5] and 8.0 [2.6-13.5] nmol/min, respectively) was accounted for entirely by the liver; release of cortisol from visceral tissues into portal vein was not detected.

CONCLUSIONS: Cortisol is released from subcutaneous adipose tissue by 11beta-HSD1 in humans, and increased enzyme expression in obesity is likely to increase local glucocorticoid signaling and contribute to whole-body cortisol regeneration. However, visceral adipose 11beta-HSD1 activity is insufficient to increase portal vein cortisol concentrations and hence to influence intrahepatic glucocorticoid signaling.

Place, publisher, year, edition, pages
2009. Vol. 58, no 1, 46-53 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-32405DOI: 10.2337/db08-0969PubMedID: 18852329OAI: diva2:303094
Available from: 2010-03-11 Created: 2010-03-11 Last updated: 2011-10-21Bibliographically approved
In thesis
1. Adipose tissue as an active organ:  blood flow regulation and tissue-specific glucocorticoid metabolism
Open this publication in new window or tab >>Adipose tissue as an active organ:  blood flow regulation and tissue-specific glucocorticoid metabolism
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Despite advances in the treatment of atherosclerosis, cardiovascular disease is the leading cause of death worldwide. With the population getting older and more obese, the burden of cardiovascular disease may further increase. Premenopausal women are relatively protected against cardiovascular disease compared to men, but the reasons for this sex difference are partly unknown. Redistribution of body fat from peripheral to central depots may be a contributing factor. Central fat is associated with hyperlipidemia, hyperglycemia, hypertension, and insulin resistance. Two possible mediators of these metabolic disturbances are tissue-specific production of the stress hormone cortisol and adipose tissue blood flow (ATBF). The aim of this thesis was to determine the adipose tissue production of cortisol by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and to investigate the regulation of ATBF.

Materials and Methods: Cortisol release was estimated by labeled cortisol infusions and tissue-specific catheterizations of subcutaneous and visceral adipose tissue (VAT) in men. We investigated ATBF by 133Xe-washout and its relation to autonomic activity, endothelial function, adipose tissue distribution, and adipokines in different groups of women. We further investigated the effect of two diets and of weight loss on ATBF in women.

Results: We demonstrated significant cortisol release from subcutaneous adipose tissue in humans. Splanchnic cortisol release was accounted for entirely by the liver. Cortisol release from VAT (to the portal vein) was not detected. ATBF decreased according to increasing weight and postmenopausal status, and the level of blood flow was associated with nitric oxide (NO) activity and autonomic activity. ATBF was also highly associated with leptin levels and both subcutaneous adipose tissue and VAT areas. After 6 months of diet and weight reduction, a significant difference in ATBF was observed between diet groups.

Conclusions: Our data for the first time demonstrate the contributions of cortisol generated from subcutaneous adipose tissue, visceral tissues, and liver by 11β-HSD1. ATBF is linked to autonomic activity, NO activity, and the amount of adipose tissue (independent of fat depot). Postmenopausal overweight women exhibited a loss of ATBF flexibility, which may contribute to the metabolic dysfunction seen in this group. Weight loss in a diet program could not increase the ATBF, although there were ATBF differences between diet groups. The results will increase understanding of adipose tissue biology and contribute to the development of treatment strategies targeting obesity and obesity-related disorders.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2011. 87 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1444
11β-hydroxysteroid dehydrogenase type 1, adipose tissue, autonomic nervous system, blood flow, cortisol, nitric oxide, weight loss.
National Category
Other Clinical Medicine
Research subject
urn:nbn:se:umu:diva-48415 (URN)978-91-7459-280-1 (ISBN)
Public defence
2011-11-11, Hörsal Betula, byggnad 6M, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Swedish Research Council
Available from: 2011-10-21 Created: 2011-10-19 Last updated: 2011-10-21Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Andersson, JonasOlsson, Tommy
By organisation
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 68 hits
ReferencesLink to record
Permanent link

Direct link