Rat plasma lipoproteins and apolipoproteins in experimental hypothyroidism

Hyperlipidemia associated with hypothyroidism is well documented in man and several animal species. The effect of hypothyroidism on apolipoprotein metabolism in the absence of complicating factors such as high cholesterol or fat content in the diet is virtually unknown. Hypothyroidism was therefore induced in male Sprague-Dawley rats by radiothyroidectomy (RTx-treated) or treatment with propylthiouracil (PTU-treated). Both treatments resulted in an over 90% decrease in circulating thyroid hormone concentrations accompanied by a 50-100% increase in plasma cholesterol and a 20-40% reduction in plasma triglyceride concentrations. Plasma apo E and apo B concentrations increased by 100% in the PTU-treated group and 40-50% in the RTx-group. Apo A-I increased 10 and 30% in the RTx- and PTU-treated rats, respectively, while the concentration of apo A-IV was not altered. A large increase in the low-density (LDL) and high-density lipoprotein (HDL) protein was observed and accompanied by a marked reduction of very low density lipoprotein (VLDL) in the hypothyroid rats. The electrophoretic pattern of plasma lipoproteins in the hypothyroid rats was changed by the appearance of a slow pre-beta band shown to be beta-VLDL. A redistribution of apo B occurred within the lipoprotein fractions. Apo B content in the VLDL fraction decreased and a large increase was noted in LDL. The major portion of the apo E and apo A-I increment was recovered in the HDL and to a lesser degree in LDL. An accumulation of apo E-rich larger HDL particles, resembling HDLc in apolipoprotein composition and distinct from the apo A-I-containing species, was observed by column chromatography. The results presented are consistent with the hypothesis that hypothyroidism in the rat may induce an accelerated production of VLDL catabolic remnants, including LDL, but at the same time reduce the rate of removal of these lipoproteins from the circulation.