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 (Tom) Scanlan, Joel R. Ehrenkranz

Research output: Contribution to journalArticle

46 Citations (Scopus)

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

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Lipoprotein Receptors
LDL Receptors
Thyroid Hormones
Cholesterol
Apolipoproteins B
Knockout Mice
Liver
Apolipoprotein B-48
Low Density Lipoprotein Receptor-Related Protein-1
Scavenger Receptors
VLDL Lipoproteins
Triiodothyronine
LDL Cholesterol
Lipoproteins
Triglycerides
Lipids
Messenger RNA
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Endocrinology

Cite this

Goldberg, I. J., Huang, L. S., Huggins, L. A., Yu, S., Nagareddy, P. R., Scanlan, T. T., & 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

Thyroid hormone reduces cholesterol via a non-LDL receptor-mediated pathway. / Goldberg, Ira J.; Huang, Li Shin; Huggins, Lesley A.; Yu, Shuiqing; Nagareddy, Prabhakara R.; Scanlan, Thomas (Tom); Ehrenkranz, Joel R.

In: Endocrinology, Vol. 153, No. 11, 01.11.2012, p. 5143-5149.

Research output: Contribution to journalArticle

Goldberg, IJ, Huang, LS, Huggins, LA, Yu, S, Nagareddy, PR, Scanlan, TT & Ehrenkranz, JR 2012, 'Thyroid hormone reduces cholesterol via a non-LDL receptor-mediated pathway', Endocrinology, vol. 153, no. 11, pp. 5143-5149. https://doi.org/10.1210/en.2012-1572
Goldberg IJ, Huang LS, Huggins LA, Yu S, Nagareddy PR, Scanlan TT et al. Thyroid hormone reduces cholesterol via a non-LDL receptor-mediated pathway. Endocrinology. 2012 Nov 1;153(11):5143-5149. https://doi.org/10.1210/en.2012-1572
Goldberg, Ira J. ; Huang, Li Shin ; Huggins, Lesley A. ; Yu, Shuiqing ; Nagareddy, Prabhakara R. ; Scanlan, Thomas (Tom) ; Ehrenkranz, Joel R. / Thyroid hormone reduces cholesterol via a non-LDL receptor-mediated pathway. In: Endocrinology. 2012 ; Vol. 153, No. 11. pp. 5143-5149.
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