Effect of fatty acids on rat liver nuclear T 3-receptor binding

Abstract

The effects of selected fatty acids (linoleic, oleic, and palmitic) on triiodothyronine (T 3)-receptor binding were compared in isolated rat hepatocytes, rat liver nuclei, and receptor protein. Scatchard analysis indicated that the inhibition of T 3-receptor binding by fatty acids was characterized by an increase in K d and no change in maximum binding capacity (MBC). In isolated receptors, the rank order of potency for inhibition was linoleic acid > oleic acid > palmitic acid. The K i for oleic acid in isolated receptors was the same as that for whole nuclei (15.4 ± 1.3 v 16.3 ± 1.9 μmol/L, respectively), indicating that the inhibition of nuclear T 3 binding is probably at the level of the receptor protein itself. In isolated hepatocytes, linoleic acid was more potent than oleic acid in inhibiting T 3 binding to nuclear receptors. Cell-associated T 3 was not affected by the presence of fatty acids, implying that cellular uptake of T 3 was not inhibited. High concentrations of fatty acids were necessary for inhibition of T 3-receptor binding in isolated hepatocytes, with linoleic acid being one to two orders of magnitude less potent in isolated hepatocytes compared with isolated receptors ( K i , 179 ± 12 v 4.4 ± 0.5 μmol/L, respectively). It is concluded that the inhibitory effect of fatty acids on T 3-receptor binding in isolated rat hepatocytes probably occurs at the level of the nuclear receptor, and does not involve an inhibition of the access of T 3 to the receptor. However, in vivo it seems unlikely that fatty acids will have access to the nuclear receptors in sufficiently high concentrations to affect T 3-receptor binding in liver cells.