Selective thyroid receptor modulation by GC-1 reduces serum lipids and stimulates steps of reverse cholesterol transport in euthyroid mice

Lisen Johansson, Mats Rudling, Thomas (Tom) Scanlan, Thomas Lundåsen, Paul Webb, John Baxter, Bo Angelin, Paolo Parini

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

Thyroid hormones [predominantly 3,5,3′-triiodo-L-thyronine (T 3)] regulate cholesterol and lipoprotein metabolism, but cardiac effects restrict their use as hypolipidemic drugs. T3 binds to thyroid hormone receptors (TRs) α and β. TRβ is the predominant isoform in liver, whereas T3 effects on heart rate are mediated mostly by TRα. Drugs that target TRβ or exhibit tissue-selective uptake may improve plasma lipid levels while sparing the heart. Here, we asked how the TRβ- and liver uptake-selective agonist GC-1 influences cholesterol and triglyceride metabolism in euthyroid mice. GC-1 treatment reduced serum cholesterol levels by 25% and serum triglycerides by 75% in chow-fed mice and also attenuated diet-induced hypercholesterolemia. GC-1 reduced plasma high-density lipoprotein cholesterol levels; increased expression of the hepatic high-density lipoprotein receptor, SR-BI; stimulated activity of cholesterol 7α-hydroxylase; and increased fecal excretion of bile acids. Collectively, these results suggest that GC-1 stimulates important steps in reverse cholesterol transport. Use of TRβ and uptake selective agonists such as GC-1 should be further explored as a strategy to improve lipid metabolism in dyslipoproteinemia.

Original languageEnglish (US)
Pages (from-to)10297-10302
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number29
DOIs
StatePublished - Jul 19 2005
Externally publishedYes

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Thyroid Hormone Receptors
Thyroid Gland
Cholesterol
Lipids
Serum
Liver
Triglycerides
Thyronines
Cholesterol 7-alpha-Hydroxylase
Hypolipidemic Agents
Dyslipidemias
Hypercholesterolemia
Bile Acids and Salts
Thyroid Hormones
Lipid Metabolism
HDL Cholesterol
GC 1 compound
Protein Isoforms
Heart Rate
Diet

Keywords

  • Bile acid
  • Lipoprotein
  • Selective modulation
  • Thyroid hormone
  • Triglycerides

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Selective thyroid receptor modulation by GC-1 reduces serum lipids and stimulates steps of reverse cholesterol transport in euthyroid mice. / Johansson, Lisen; Rudling, Mats; Scanlan, Thomas (Tom); Lundåsen, Thomas; Webb, Paul; Baxter, John; Angelin, Bo; Parini, Paolo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 29, 19.07.2005, p. 10297-10302.

Research output: Contribution to journalArticle

Johansson, Lisen ; Rudling, Mats ; Scanlan, Thomas (Tom) ; Lundåsen, Thomas ; Webb, Paul ; Baxter, John ; Angelin, Bo ; Parini, Paolo. / Selective thyroid receptor modulation by GC-1 reduces serum lipids and stimulates steps of reverse cholesterol transport in euthyroid mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 29. pp. 10297-10302.
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