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甲状腺转录因子-1 通过下丘脑的黑皮质素途径调节摄食行为。

Thyroid transcription factor-1 regulates feeding behavior via melanocortin pathway in the hypothalamus.

机构信息

Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.

出版信息

Diabetes. 2011 Mar;60(3):710-9. doi: 10.2337/db10-0183. Epub 2011 Jan 31.

DOI:10.2337/db10-0183
PMID:21282365
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3046831/
Abstract

OBJECTIVE

α-Melanocyte-stimulating hormone (α-MSH) and agouti-related peptide (AgRP) control energy homeostasis by their opposing actions on melanocortin receptors (MC3/4R) in the hypothalamus. We previously reported that thyroid transcription factor-1 (TTF-1) controls feeding behavior in the hypothalamus. This study aims to identify the function of TTF-1 in the transcriptional regulation of AgRP and α-MSH synthesis for the control of feeding behavior.

RESEARCH DESIGN AND METHODS

TTF-1 activity in AgRP and pro-opiomelanocortin (POMC) transcription was examined using gel-shift and promoter assays and an in vivo model of TTF-1 synthesis inhibition by intracerebroventricular injection of an antisense (AS) oligodeoxynucleotide (ODN). Double immunohistochemistry was performed to colocalize TTF-1 and AgRP or α-MSH in the hypothalamic arcuate nucleus (ARC). To determine whether TTF-1 action on food intake is mediated through MC3/4R, we measured changes in food intake upon intracerebroventricular injection of MC3/4R antagonists (SHU9119 and AgRP) into rat brain preinjected with the AS ODN.

RESULTS

TTF-1 stimulated AgRP but inhibited POMC transcription by binding to the promoters of these genes. TTF-1 was widely distributed in the hypothalamus, but we identified some cells coexpressing TTF-1 and AgRP or α-MSH in the ARC. In addition, intracerebroventricular administration of leptin decreased TTF-1 expression in the hypothalamus, and AS ODN-induced inhibition of TTF-1 expression decreased food intake and AgRP expression but increased α-MSH expression. Anorexia induced by the AS ODN was attenuated by the administration of MC3/4R antagonists.

CONCLUSIONS

TTF-1 transcriptionally regulates synthesis of AgRP and α-MSH in the ARC and affects feeding behavior via the melanocortin pathway.

摘要

目的

α-促黑素细胞激素（α-MSH）和刺鼠相关肽（AgRP）通过在下丘脑的黑素皮质素受体（MC3/4R）上的拮抗作用来控制能量稳态。我们之前报道过甲状腺转录因子-1（TTF-1）控制下丘脑的摄食行为。本研究旨在确定 TTF-1 在 AgRP 和 α-MSH 合成的转录调控中的作用，以控制摄食行为。

研究设计和方法

使用凝胶迁移和启动子测定以及通过脑室内注射反义（AS）寡脱氧核苷酸（ODN）抑制 TTF-1 合成的体内模型，检查 TTF-1 在 AgRP 和前阿黑皮素原（POMC）转录中的活性。进行双重免疫组织化学染色以在下丘脑弓状核（ARC）中使 TTF-1 和 AgRP 或 α-MSH 共定位。为了确定 TTF-1 对食物摄入的作用是否通过 MC3/4R 介导，我们测量了在向预先注射了 AS ODN 的大鼠脑室内注射 MC3/4R 拮抗剂（SHU9119 和 AgRP）后食物摄入的变化。

结果

TTF-1 通过与这些基因的启动子结合刺激 AgRP 但抑制 POMC 转录。TTF-1 在下丘脑广泛分布，但我们在 ARC 中鉴定出一些共表达 TTF-1 和 AgRP 或 α-MSH 的细胞。此外，脑室内给予瘦素可降低下丘脑 TTF-1 的表达，而 TTF-1 表达的 AS ODN 抑制可减少食物摄入和 AgRP 的表达，但增加 α-MSH 的表达。MC3/4R 拮抗剂的给药可减轻 AS ODN 诱导的厌食症。

结论

TTF-1 在 ARC 中转录调节 AgRP 和 α-MSH 的合成，并通过黑素皮质素途径影响摄食行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/6f6c553ecff2/710fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/d48847582387/710fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/94a93e367ee2/710fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/ca74d2ae1894/710fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/7a075a9e2d5f/710fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/1b1a4a2fcf10/710fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/44e6d726e099/710fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/6f6c553ecff2/710fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/d48847582387/710fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/797ab078585f/710fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/94a93e367ee2/710fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/ca74d2ae1894/710fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/7a075a9e2d5f/710fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/1b1a4a2fcf10/710fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/44e6d726e099/710fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4db/3046831/6f6c553ecff2/710fig8.jpg

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本文引用的文献

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2
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Trends Endocrinol Metab. 2009 Jul;20(5):203-15. doi: 10.1016/j.tem.2009.02.002. Epub 2009 Jun 21.
3
Thyroid-specific enhancer-binding protein Role in thyroid function and organogenesis.甲状腺特异性增强子结合蛋白在甲状腺功能和器官发生中的作用。
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4
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5
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6
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7
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4
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9
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10
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