An oxidized derivative of linoleic acid affects aldosterone secretion by adrenal cells in vitro.

Based on the clinical observation that humans with visceral adiposity have higher plasma aldosterone levels than controls, we postulated that endogenous fatty acids can be oxidized by the liver to form stimuli of the adrenal cortex. Although we could show that hepatocytes produced adrenal stimuli from linoleic acid in vitro, the yield was very small. To facilitate the elucidation of chemical structures, we incubated a large amount of linoleic acid with lipoxygenase, then treated the hydroperoxide with cysteine and iron. The major product of this process was 12,13-epoxy-9-keto-10-trans-octadecenoic acid. This epoxy-keto compound stimulated aldosterone production at concentrations from 0.5 to 15 microm. At higher concentrations, it was inhibitory. The epoxy-keto-octadecenoic acid exhibited the chromatographic characteristics of one product of the incubation of linoleic acid with hepatocytes. The results are consistent with the postulated conversion of linoleic acid to stimuli of aldosterone production. This may be a mechanistic link between visceral obesity and hypertension in humans.