Thyroid hormone-stimulated increases in PGC-1α and UCP2 promote life history-specific endocrine changes and maintain a lipid-based metabolism.
Thyroid hormone-stimulated increases in PGC-1α and UCP2 promote life history-specific endocrine changes and maintain a lipid-based metabolism.
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甲状腺激素刺激的 PGC-1α 和 UCP2 增加促进生活史特异性内分泌变化并维持基于脂质的代谢。
DOI：
10.1152/ajpregu.00395.2016
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Ortiz,RudyM
中科院分区：
文献类型：
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作者：
Martinez,Bridget;Soñanez-Organis,JoséG;Godoy-Lugo,JoséArquimides;Horin,LillianJ;Crocker,DanielE;Ortiz,RudyM
甲状腺激素（THs）调节新陈代谢，但通常在紧张的生理条件下被抑制，包括禁食。有趣的是，北方象海豹幼崽的长时间禁食与依赖脂质代谢和循环三手环水平增加有关，这部分归因于活跃的分泌，而不是减少的清除。这种明显的矛盾与细胞促肾上腺素介导的活性的互补增加相结合，表明在自然适应长时间禁食的哺乳动物中，促肾上腺素是支持新陈代谢所必需的。然而，这种生理悖论的功能相关性在很大程度上仍未被探索，特别是当它与脂质调节有关时。为了解决TSH介导的this增加有助于脂质代谢的假设，我们向早期和晚期禁食的幼崽注入TSH，并测量脂肪和肌肉中的几个关键基因，以及与脂质代谢调节相关的血浆激素。TSH输注使肌肉中过氧化物酶体增殖物激活受体γ共激活因子-1α (PGC-1α) mRNA表达在60 min时增加了6.5倍以上，脂肪中解偶联蛋白2 (UCP2) mRNA表达在60 min时增加了27倍以上。此外，在禁食后期，脂肪CD36的蛋白质含量增加了1.1倍，血浆非酯化脂肪酸（NEFA）浓度在120分钟内增加了25%，24小时后NEFA水平恢复到基线水平。我们发现，tsh诱导的禁食幼崽中THs的增加是功能性的，可能有助于维持基于脂质的代谢。
Thyroid hormones (THs) regulate metabolism, but are typically suppressed during times of stressful physiological conditions, including fasting. Interestingly, prolonged fasting in northern elephant seal pups is associated with reliance on a lipid-based metabolism and increased levels of circulating THs that are partially attributed to active secretion as opposed to reduced clearance. This apparent paradox is coupled with complementary increases in cellular TH-mediated activity, suggesting that in mammals naturally adapted to prolonged fasting, THs are necessary to support metabolism. However, the functional relevance of this physiological paradox has remained largely unexplored, especially as it relates to the regulation of lipids. To address the hypothesis that TSH-mediated increase in THs contributes to lipid metabolism, we infused early and late-fasted pups with TSH and measured several key genes in adipose and muscle, and plasma hormones associated with regulation of lipid metabolism. TSH infusion increased the mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) more than 6.5-fold at 60 min in muscle, and expression of uncoupling protein 2 (UCP2) more than 27-fold during the early fast at 60 min, in adipose. Additionally, during the late fast period, the protein content of adipose CD36 increased 1.1-fold, and plasma nonesterified fatty acid (NEFA) concentrations increased 25% at 120 min, with NEFA levels returning to baseline after 24 h. We show that the TSH-induced increases in THs in fasting pups are functional and likely contribute to the maintenance of a lipid-based metabolism.