title: Thyroid hormone reduces cholesterol via a non-LDL receptor-mediated pathway.
abstract: Although studies in vitro and in hypothyroid animals show that thyroid hormone can, under some circumstances, modulate the actions of low-density lipoprotein (LDL) receptors, the mechanisms responsible for thyroid hormone's lipid-lowering effects are not completely understood. We tested whether LDL receptor (LDLR) expression was required for cholesterol reduction by treating control and LDLR-knockout mice with two forms of thyroid hormone T(3) and 3,5-diiodo-l-thyronine. High doses of both 3,5-diiodo-l-thyronine and T(3) dramatically reduced circulating total and very low-density lipoprotein/LDL cholesterol (∼70%) and were associated with reduced plasma T(4) level. The cholesterol reduction was especially evident in the LDLR-knockout mice. Circulating levels of both apolipoprotein B (apo)B48 and apoB100 were decreased. Surprisingly, this reduction was not associated with increased protein or mRNA expression of the hepatic lipoprotein receptors LDLR-related protein 1 or scavenger receptor-B1. Liver production of apoB was markedly reduced, whereas triglyceride production was increased. Thus, thyroid hormones reduce apoB lipoproteins via a non-LDLR pathway that leads to decreased liver apoB production. This suggests that drugs that operate in a similar manner could be a new therapy for patients with genetic defects in the LDLR.
authors.affiliation: Department of Medicine, Columbia University, New York, New York 10032, USA. ijg3@columbia.edu
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
authors.forename: Li-Shin
authors.initials: LS
authors.lastname: Huang
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Huggins
authors.forename: Shuiqing
authors.initials: S
authors.lastname: Yu
authors.forename: Prabhakara R
authors.initials: PR
authors.lastname: Nagareddy
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Scanlan
authors.forename: Joel R
authors.initials: JR
authors.lastname: Ehrenkranz
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D004104:Diiodothyronines / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D001055:Apolipoproteins B; D004104:Diiodothyronines; D011973:Receptors, LDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014284:Triiodothyronine; C030103:3,5-diiodothyronine; D002784:Cholesterol; D013974:Thyroxine