Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Thyroid. 2012 Feb;22(2):192-9. doi: 10.1089/thy.2011.0289. Epub 2011 Dec 16.
Decreased serum leptin has been proposed as a critical signal initiating the neuroendocrine response to fasting. Leptin administration partially reverses the fasting-induced suppression of the hypothalamus-pituitary-thyroid axis at the central level. It is, however, unknown to what extent leptin affects peripheral thyroid hormone metabolism. The aim of this study was to evaluate the effect of leptin administration on starvation-induced alterations of peripheral thyroid hormone metabolism in mice.
Three types of experiments were performed: (i) mice were fasted for 24 hours while leptin was administered twice (at 0 and 8 hours, 1 μg/g body weight [BW]), (ii) mice were fasted for 24 hours and, subsequently, leptin was given once at 24 hours (killed at 28 and 32 hours), and (iii) mice were fasted for 48 hours. All groups had appropriate controls. Serum triiodothyronine and thyroxine, liver type 1 deiodinase (D1), type 3 deiodinase (D3), thyroid hormone receptor (TR)β1, TRα1 and α2 mRNA expression, and liver D1 and D3 activity were measured.
Twenty-four hours of fasting decreased liver TRβ1 mRNA expression, while liver TRα1, TRα2, and D1 mRNA expression and activity did not change. In contrast, 24 hours of fasting increased liver D3 mRNA. Leptin administration after fasting restored liver D3 expression, while serum thyroid hormone levels and liver TRβ1 expression remained low.
Leptin administration selectively restores starvation-induced increased hepatic D3 expression independently of serum thyroid hormone concentrations. The present study shows that fasting-induced changes in mRNA expression of genes involved in hepatic hormone metabolism are influenced not only by decreased serum thyroid hormone levels but also by serum leptin.
血清瘦素水平降低被认为是启动禁食引起的神经内分泌反应的关键信号。瘦素给药在中枢水平部分逆转了禁食引起的下丘脑-垂体-甲状腺轴的抑制。然而，瘦素对周围甲状腺激素代谢的影响程度尚不清楚。本研究旨在评估瘦素给药对饥饿诱导的小鼠周围甲状腺激素代谢改变的影响。
进行了三种类型的实验：（i）小鼠禁食 24 小时，同时两次给予瘦素（0 小时和 8 小时，1μg/g 体重），（ii）小鼠禁食 24 小时，随后在 24 小时时给予一次瘦素（在 28 小时和 32 小时处死），和（iii）小鼠禁食 48 小时。所有组均有适当的对照。测量血清三碘甲状腺原氨酸和甲状腺素、肝脏 1 型脱碘酶（D1）、3 型脱碘酶（D3）、甲状腺激素受体（TR）β1、TRα1 和α2 mRNA 表达以及肝脏 D1 和 D3 活性。
24 小时禁食降低了肝脏 TRβ1 mRNA 表达，而肝脏 TRα1、TRα2 和 D1 mRNA 表达和活性没有变化。相反，24 小时禁食增加了肝脏 D3 mRNA。禁食后给予瘦素恢复了肝脏 D3 的表达，而血清甲状腺激素水平和肝脏 TRβ1 表达仍较低。
瘦素给药选择性地恢复了饥饿引起的肝脏 D3 表达增加，而与血清甲状腺激素浓度无关。本研究表明，参与肝脏激素代谢的基因的 mRNA 表达的变化不仅受血清甲状腺激素水平降低的影响，还受血清瘦素的影响。
