期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：29
页码：10297-10302
DOI：10.1073/pnas.0504379102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Thyroid hormones [predominantly 3,5,3'-triiodo-L-thyronine (T3)] regulate cholesterol and lipoprotein metabolism, but cardiac effects restrict their use as hypolipidemic drugs. T3 binds to thyroid hormone receptors (TRs) {alpha} and {beta}. TR{beta} is the predominant isoform in liver, whereas T3 effects on heart rate are mediated mostly by TR{alpha}. Drugs that target TR{beta} or exhibit tissue-selective uptake may improve plasma lipid levels while sparing the heart. Here, we asked how the TR{beta}- 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 7{alpha}-hydroxylase; and increased fecal excretion of bile acids. Collectively, these results suggest that GC-1 stimulates important steps in reverse cholesterol transport. Use of TR{beta} and uptake selective agonists such as GC-1 should be further explored as a strategy to improve lipid metabolism in dyslipoproteinemia.
