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New insights into regulation of lipid metabolism by thyroid hormone

Zhu, Xuguang; Cheng, Sheue-yann

Current Opinion in Endocrinology, Diabetes and Obesity: October 2010 - Volume 17 - Issue 5 - p 408–413
doi: 10.1097/MED.0b013e32833d6d46
Thyroid: Edited by Paul J. Davis
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Purpose of review Thyroid hormone (3,3′,5-triiodo-L-thyronine) plays an important role in thermogenesis and maintenance of lipid homeostasis. The present article reviews the evidence that 3,3′,5-triiodo-L-thyronine regulates lipid metabolism via thyroid hormone receptors, focusing particularly on in-vivo findings using genetically engineered mice.

Recent findings That lipid metabolism is regulated via thyroid hormone receptor isoforms in a tissue-dependent manner was recently uncovered by using knockin mutant mice harboring an identical mutation in the Thra gene (Thra1PV mouse) or the Thrb gene (ThrbPV mouse). The mutation in the Thra gene dramatically decreases the mass of both white adipose tissue and liver. In contrast, the mutation in the Thrb gene markedly increases the mass of liver with an excess depot of lipids, but no significant abnormality is observed in white adipose tissue. Molecular studies show that the expression of lipogenic genes is decreased in white adipose tissue of Thra1PV mice, but not in ThrbPV mice. Markedly increased lipogenic enzyme expression, and decreased fatty acid beta-oxidation activity contribute to the adipogenic steatosis and lipid accumulation in the liver of ThrbPV mice. In contrast, reduced expression of genes critical for lipogenesis mediates decreased liver mass with lipid scarcity in Thra1PV mice.

Summary Studies using Thra1PV and ThrbPV mice indicate that apo-thyroid hormone receptor-beta and apo-thyroid hormone receptor-alpha-1 mediate distinct deleterious effects on lipid metabolism. Thus, both thyroid hormone receptor isoforms contribute to the pathogenesis of lipid abnormalities in hypothyroidism, but in a target tissue-dependent manner. These studies suggest that thyroid hormone receptor isoform-specific ligands could be designed as therapeutic targets for lipid abnormalities.

Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Correspondence to Dr Sheue-yann Cheng, Laboratory of Molecular Biology, National Cancer Institute, 37 Convent Drive, Room #5128, Bethesda, MD 20892-4264, USA Tel: +1 301 496 4280; fax: +1 301 402 1344; e-mail: chengs@mail.nih.gov

© 2010 Lippincott Williams & Wilkins, Inc.