HDL biology
Thyroid hormone excess doubles CETP activity and accelerates HDL clearance in transgenic mice (Metabolism 2001)
Original title: Thyroid hormone increases plasma cholesteryl ester transfer protein activity and plasma high-density lipoprotein removal rate in transgenic mice
In hypothyroid and hyperthyroid CETP-transgenic and nontransgenic mice, hyperthyroid transgenic mice showed a significant rise in VLDL (P less than .001) and a fall in HDL (P less than .005), while hypothyroid transgenic mice showed a rise in LDL (P less than .02). Hyperthyroid transgenic mice had twice the plasma CETP activity of controls, unchanged in hypothyroid mice, and nontransgenic wild-type mice showed no lipoprotein-profile change with thyroid status, confirming CETP's role. HDL fractional removal rate was about 2-fold faster in hyperthyroid transgenic mice, with postheparin hepatic lipase activity reduced (P less than .05), showing that thyroid hormone excess accelerates HDL metabolism mainly through increased CETP activity, independent of hepatic lipase.
Original abstract
Thyroid dysfunction produces multiple alterations in plasma lipoprotein levels, including high-density lipoprotein (HDL). Cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are important proteins that modulate the metabolism of HDL. Thus, the effect of thyroid hormone on the activities of CETP and of HL was investigated using hypothyroid and hyperthyroid CETP transgenic (Tg) and nontransgenic (nTg) mice. Hyperthyroid Tg mice plasma lipoprotein (LP) profile analysis showed a significant increase in the very-low-density lipoprotein (VLDL) fraction (P <.001) and decrease in the HDL fraction (P <.005), whereas in the hypothyroid Tg mice an increase in low-density lipoprotein (LDL) was observed (P <.02). CETP activity was measured as the transfer of (14)C-cholesteryl ester (CE) from labeled HDL to LDL by an isotopic assay indicative of mass. Hyperthyroid Tg mice had twice as much plasma CETP activity as compared with their controls, while in hypothyroid Tg mice plasma CETP activity did not change. The role of CETP in determining the changes in LP profile of hyperthyroid animals was confirmed by showing that nTg wild-type hyperthyroid and euthyroid mice exhibited the same percent cholesterol distribution in LP. Postheparin HL activity measured in hyperthyroid Tg mice was significantly reduced (P <.05). (3)H-cholesteryl oleoyl ether ((3)H-Cet)-HDL plasma fractional removal rate (FRR) was approximately 2-fold faster in the hyperthyroid Tg mice than in controls, but was not modified in hypothyroid animals. Tissue uptake of (3)H-Cet was examined in 10 tissue samples: levels were significantly increased in skeletal muscle and decreased in small intestine in hyperthyroid Tg mice, and decreased in the small intestine of hypothyroid Tg mice. In conclusion, the excess of thyroid hormone accelerates HDL metabolism in CETP transgenic mice mainly due to an increase in plasma CETP activity and independently from the HL activity. Hypothyroid status did not change CETP activity and HDL metabolism.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.