Tissue selective modulation of redox and phosphate potentials by beta,beta'-methyl-substituted hexadecanedioic acid.

Abstract

beta,beta'-Methyl-substituted hexadecanedioic acid (MEDICA 16) shares some of the calorigenic-hypolipidemic characteristics of thyroid hormones. In light of this similarity, MEDICA 16 was further evaluated here as a modulator of rat liver redox and phosphate potentials as well as an effector of cardiac high energy intermediates level in comparison to thyroid hormone. 1) Similarly to thyroid hormone, MEDICA 16 treatment resulted in 3.5-fold decrease in cytosolic redox potential. With both treatment modes, the induced decrease in cytosolic redox potential resulted in a concomitant increase in the liver capacity of handling an ethanol or xylitol load. 2) The apparent liver cytosolic phosphate potential calculated from the glycerol-3-phosphate 3-phosphoglyceric acid ratio evaluated under conditions of rapid equilibrium within the glycerol-3 phosphate/3-phosphoglyceric acid metabolic section was found to remain unaffected by either MEDICA 16 or T3 treatment. However, the apparent cellular phosphate potential was substantially decreased by both treatment modes, thus reflecting a decrease in the apparent liver mitochondrial phosphate potential. 3) Similarly to thyroid hormone, the effect of MEDICA 16 on liver redox and phosphate potentials could be accounted for by induction of mitochondrial glycerol-3-phosphate dehydrogenase. 4) In contrast to liver, heart high energy intermediates were affected by thyroid hormone but not by MEDICA 16 treatment. 5) The effect of T3 and MEDICA 16 with respect to liver redox and phosphate potentials may partially account for the calorigenic-hypolipidemic effect of both. MEDICA 16 may however serve as a selective liver thyromimetic agent lacking the cardiac affect induced by thyroid hormone.