Thyroid hormone reduces cholesterol via a non-LDL receptor-mediated pathway

Ira J. Goldberg, Li Shin Huang, Lesley A. Huggins, Shuiqing Yu, Prabhakara R. Nagareddy, Thomas S. Scanlan, Joel R. Ehrenkranz

Research output: Contribution to journalArticle

51 Scopus citations

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 T3 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 T4 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 anon-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.

Original languageEnglish (US)
Pages (from-to)5143-5149
Number of pages7
JournalEndocrinology
Volume153
Issue number11
DOIs
StatePublished - Nov 1 2012

ASJC Scopus subject areas

  • Endocrinology

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    Goldberg, I. J., Huang, L. S., Huggins, L. A., Yu, S., Nagareddy, P. R., Scanlan, T. S., & Ehrenkranz, J. R. (2012). Thyroid hormone reduces cholesterol via a non-LDL receptor-mediated pathway. Endocrinology, 153(11), 5143-5149. https://doi.org/10.1210/en.2012-1572