Thyroid hormone increases plasma cholesteryl ester transfer protein activity and plasma high-density lipoprotein removal rate in transgenic mice

Thyroid dysfunction produces multiple alterations in plasma lipoprotein lev els, including high-density lipoprotein (HDL). Cholesteryl ester transfer p rotein (CETP) and hepatic lipase (HL) are important proteins that modulate the metabolism of HDL. Thus, the effect of thyroid hormone on the activitie s of CETP and of HL was investigated using hypothyroid and hyperthyroid CET P transgenic (Tg) and nontransgenic (nTg) mice. Hyperthyroid Tg mice plasma lipoprotein (LP) profile analysis showed a significant increase in the ver y-low-density lipoprotein (VLDL) fraction (P < .001) and decrease in the HD L fraction (P < .005). whereas in the hypothyroid Tg mice an increase in lo w-density lipoprotein (LDL) was observed (P < .02). CETP activity was measu red as the transfer of C-14-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 hypothy roid Tg mice plasma CETP activity did not change. The role of CETP in deter mining the changes in LP profile of hyperthyroid animals was confirmed by s howing that nTg wild-type hyperthyroid and euthyroid mice exhibited the sam e percent cholesterol distribution in LP. Postheparin HL activity measured in hyperthyroid Tg mice was significantly reduced (P < .05). H-3-cholestery l oleoyl ether (H-3-Cet)-HDL plasma fractional removal rate (FRR) was appro ximately 2-fold faster in the hyperthyroid Tg mice than in controls, but wa s not modified in hypothyroid animals. Tissue uptake of H-3-Cet was examine d in 10 tissue samples: levels were significantly increased in skeletal mus cle and decreased in small intestine in hyperthyroid Tg mice, and decreased in the small intestine of hypothyroid Tg mice. In conclusion, the excess o f thyroid hormone accelerates HDL metabolism in CETP transgenic mice mainly due to an increase in plasma CETP activity and independently from the HL a ctivity. Hypothyroid status did not change CETP activity and HDL metabolism . Copyright (C) 2001 by W.B. Saunders Company.