Adipo-adrenocortical Co-cultures

Abstract

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 aldosterone levels. 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 sevenfold over 24 h of incubation. This stimulation was comparable to maximal stimulation of these cells with forskolin (2 × 10– 5 M). On the molecular level, there was a tenfold increase in steroid acute regulatory peptide (StAR) mRNA expression. This effect was independent of adipose angiotensin II as revealed by the stimulatory effect of fat cell-conditioned medium (FCCM), even in the presence of the angiotensin type 1 receptor antagonist, valsartan. None of the adipocytokines recently defined accounted for the effect. Mineralocorticoid-stimulating activity was heat-sensitive and could be blunted by heating FCCM to 99°C. Centrifugal filtration based on molecular weight revealed at least two releasing factors. A heat sensitive fraction (MW > 50 kD) representing 60% of total activity and an inactive fraction (MW < 50 kD). However, the recovery rate increased to 92% on combining these two fractions, indicating the interaction of least two factors. In conclusion, human adipocytes secrete potent mineralocorticoid releasing factors, suggesting a novel direct link between obesity and hypertension.