Formation of the very low density lipoprotein and metabolism of [1- 14C]-oleate by perfused livers from rats treated with triiodothyronine or propylthiouracil

Abstract

To gain insight into the mechanism(s) responsible for changes in plasma lipid concentrations in thyroid disease, the metabolism of [1- 14C]-oleate by perfused livers from hypothyroid [propylthiouracil (PTU) treated], euthyroid and hyperthyroid (T 3 treated) rats was compared. Livers from hyperthyroid animals secreted decreased amounts of very low density lipoprotein (VLDL) and incorporated less [1- 14C]-oleate into VLDL triglyceride, but produced more ketone bodies and incorporated more radioactivity from [1- 14C]-oleate into ketones than did livers from euthyroid animals. Conversely, incorporation of [1- 14C]-oleate into perfusate and VLDL triglyceride was increased in livers from hypothyroid animals, while rates of production of 14CO 2 were diminished. Plasma T 3 concentration was inversely correlated with VLDL triglyceride ( r = −0.70, p < 0.003) and VLDL apoprotein ( r = −0.72, p < 0.008), but directly correlated with ketogenesis ( r = 0.71, p < 0.002). Thyroid hormone diminished esterification of fatty acids, and inhibited the hepatic production of triglyceride and secretion of VLDL and stimulated ketogenesis, whereas thyroid hormone deficiency increased hepatic esterification of fatty acid to triglyceride, tended to increase output of the VLDL, and diminished oxidation of fatty acid through the tricarboxylic acid cycle. The surface lipid (phospholipid, cholesterol) to apoprotein ratio was directly correlated with the output of VLDL triglyceride ( r = 0.85, p < 0.0005). Furthermore, the lipid composition of the secreted VLDL particle was influenced by thyroid status. Plasma T 3 concentration was directly correlated with the molar ratios of phospholipid/triglyceride ( r = 0.73, p < 0.001), cholesterol/triglyceride ( r = 0.85, p < 0.0001), and cholesteryl ester/triglyceride ( r = 0.80, p < 0.0002) in the VLDL particle. A direct correlation was also demonstrable between the ratio apoprotein/triglyceride and plasma T 3 concentration ( r = 0.72, p < 0.0084), while the ratio was inversely correlated with output of VLDL triglyceride ( r = −0.76, p < 0.0038). The percentage of certain of the polymorphic forms of arginine-rich peptide was increased, while apo C-III 3 was decreased in VLDL produced by livers from hypothyroid rats. These data are consistent with the hypothesis that as output of VLDL diminished in the progression from hypothyroidism to hyperthyroidism, the VLDL particle secreted became smaller with a larger ratio of surface to core components.