Inhibition by 5-(tetradecyloxy)-2-furoic acid of fatty acid and cholesterol synthesis in isolated rat hepatocytes

Abstract

Fatty acid and cholesterol synthesis in isolated rat hepatocytes were strongly inhibited by 5-(tetradecyloxy)-2-furoic acid. With either 3H2O or [2(-14)C] acetate as the labeled precursor, the concentrations of inhibitor causing 50% decrease in fatty acid and cholesterol synthesis were, respectively, less than 0.005 mM and 0.020 mM. At 0.1 mM inhibitor, citrate concentration in cells from fed rats was increased by 75%; lactate and pyruvate concentrations were decreased by 30%; ethanol oxidation was decreased by 20%; with cells from starved rats, the mitochondrial [NAD+]/[NADH] was decreased. Other parameters were unaffected. Both its potency and its specificity indicate that 5-(tetradecyloxy)-2-furoic acid will be useful in studies on the regulation of lipid biosynthesis.