甲状腺激素调节脂质代谢的新见解。,Current Opinion in Endocrinology, Diabetes and Obesity

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甲状腺激素调节脂质代谢的新见解。
Current Opinion in Endocrinology, Diabetes and Obesity ( IF 2.6 ) Pub Date : 2010-10-01 , DOI: 10.1097/med.0b013e32833d6d46
Xuguang Zhu ₁ , Sheue-yann Cheng

Affiliation

综述目的甲状腺激素（3,3',5-triiodo-L-thyronine）在产热和维持脂质体内平衡中起重要作用。本文回顾了 3,3',5-三碘-L-甲状腺氨酸通过甲状腺激素受体调节脂质代谢的证据，特别关注使用基因工程小鼠的体内发现。最近的发现最近通过使用在 Thra 基因（Thra1(PV) 小鼠）或 Thrb 基因（Thrb(PV)鼠）。Thra 基因的突变显着降低了白色脂肪组织和肝脏的质量。相比之下，Thrb 基因的突变显着增加了肝脏的质量，并具有过多的脂质库，但在白色脂肪组织中未观察到明显异常。分子研究表明，Thra1(PV) 小鼠的白色脂肪组织中脂肪生成基因的表达降低，但 Thrb(PV) 小鼠没有。显着增加的脂肪生成酶表达和降低的脂肪酸 β-氧化活性有助于 Thrb(PV) 小鼠肝脏中的脂肪生成和脂质积累。相比之下，在 Thra1(PV) 小鼠中，脂肪生成关键基因的表达减少介导了肝脏质量减少和脂质稀缺。总结使用 Thra1(PV) 和 Thrb(PV) 小鼠的研究表明，apo-甲状腺激素受体-β 和 apo-甲状腺激素受体-α-1 介导对脂质代谢的明显有害影响。因此，这两种甲状腺激素受体亚型都有助于甲状腺功能减退症脂质异常的发病机制，但以目标组织依赖性方式。这些研究表明，甲状腺激素受体亚型特异性配体可以设计为脂质异常的治疗靶点。

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New insights into regulation of lipid metabolism by thyroid hormone.

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 (Thra1(PV) mouse) or the Thrb gene (Thrb(PV) 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 Thra1(PV) mice, but not in Thrb(PV) 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 Thrb(PV) mice. In contrast, reduced expression of genes critical for lipogenesis mediates decreased liver mass with lipid scarcity in Thra1(PV) mice. SUMMARY Studies using Thra1(PV) and Thrb(PV) 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.

更新日期：2019-11-01

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