Document Detail

Human adipocytes secrete mineralocorticoid-releasing factors.
MedLine Citation:
PMID:  14614137     Owner:  NLM     Status:  MEDLINE    
Obesity has become an epidemic problem in western societies, contributing to metabolic diseases, hypertension, and cardiovascular disease. Overweight and obesity are frequently associated with increased plasma levels of aldosterone. Recent evidence suggests that human fat is a highly active endocrine tissue. Therefore, we tested the hypothesis that adipocyte secretory products directly stimulate adrenocortical aldosterone secretion. Secretory products from isolated human adipocytes strongly stimulated steroidogenesis in human adrenocortical cells (NCI-H295R) with a predominant effect on mineralocorticoid secretion. Aldosterone secretion increased 7-fold during 24 h of incubation. This stimulation was comparable to maximal stimulation of these cells with forskolin (2 x 10(-5) M). On the molecular level, there was a 10-fold increase in the expression of steroid acute regulatory peptide mRNA. This effect was independent of adipose angiotensin II as revealed by the stimulatory effect of fat cell-conditioned medium even in the presence of the angiotensin type 1 receptor antagonist, valsartan. None of the recently defined adipocytokines accounted for the effect. Mineralocorticoid-stimulating activity was heat sensitive and could be blunted by heating fat cell-conditioned medium to 99 degrees C. Centrifugal filtration based on molecular mass revealed at least two releasing factors: a heat sensitive fraction (molecular mass >50 kDa) representing 60% of total activity, and an inactive fraction (molecular mass <50 kDa). However, the recovery rate increased to 92% when combining these two fractions, indicating the interaction of at least two factors. In conclusion, human adipocytes secrete potent mineralocorticoid-releasing factors, suggesting a direct link between obesity and hypertension.
M Ehrhart-Bornstein; V Lamounier-Zepter; A Schraven; J Langenbach; H S Willenberg; A Barthel; H Hauner; S M McCann; W A Scherbaum; S R Bornstein
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-11-12
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  100     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-12-03     Completed Date:  2004-02-02     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14211-6     Citation Subset:  IM    
German Diabetes Center, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
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MeSH Terms
Adipocytes / drug effects,  secretion*
Adrenal Cortex / physiopathology
Aldosterone / secretion
Angiotensin II / physiology
Base Sequence
Culture Media, Conditioned
Forskolin / pharmacology
Hot Temperature
Hypertension / etiology,  physiopathology
Mineralocorticoids / secretion*
Models, Biological
Obesity / etiology,  physiopathology
Phosphoproteins / genetics
RNA, Messenger / genetics,  metabolism
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Mineralocorticoids; 0/Phosphoproteins; 0/RNA, Messenger; 0/steroidogenic acute regulatory protein; 11128-99-7/Angiotensin II; 52-39-1/Aldosterone; 66428-89-5/Forskolin

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