ODP147 Free fatty acids stimulate aldosterone secretion in human adrenal carcinoma HAC15 cells

Primary hyperaldosteronism (PA) accounts for 5-10% of hypertension overall and up to 35% in people with obesity and sleep apnea. It has been postulated that the hyperaldosteronism, in these latter cases, is induced by factors independent of renin/angiotensin activation, but rather through soluble molecules associated with obesity. It has been shown that in obesity, free fatty acids (FFA) are associated with insulin resistance and hypertension. To test the relationship of free fatty acids with aldosterone synthesis, the human adrenal cell line HAC15, which has been extensively studied for adrenal steroidogenesis, was evaluated with regard to both aldosterone (ALDO) synthesis (by ELISA) and the induction of the rate limiting enzyme for aldosterone synthesis (CYP11B2, by quantitative PCR and Western blot). HAC15 responded appropriately to stimulation by angiotensin 2 (AII) with a 2.1-fold rise in ALDO. When this system was challenged with palmitate at 0.8 mM, there was a 1.8-fold increase in ALDO and 8-fold increase in CYP11B2 at mRNA and protein levels. These increases were not associated with the likelihood that the FFA were simply providing metabolic substrate as the effect was not blocked by the carnitine palmitoyltransferase 1 (CPT1) inhibitor etomoxir. However, palmitate treatment when compared to controls, was associated with ER stress, as measured by a four-fold induction of ER stress marker C/-EBP homologous protein mRNA, and with mitochondrial membrane dysfunction, as measured by a 24% decrease of Tetramethylrhodamine, ethyl ester (TMRE) fluorescence. These results suggest that in people with obesity and insulin resistance, FFA may augment or precipitate a state of primary hyperaldosteronism. Further studies are warranted to explore the underlying mechanisms of FFA augmentation of ALDO and its clinical significance. Presentation: No date and time listed