Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, A Coruña, Spain.
Nat Med. 2010 Sep;16(9):1001-8. doi: 10.1038/nm.2207. Epub 2010 Aug 29.
Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here we demonstrate that either whole-body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS) activity and upregulates thermogenic markers in brown adipose tissue (BAT). Inhibition of the lipogenic pathway in the ventromedial nucleus of the hypothalamus (VMH) prevents CNS-mediated activation of BAT by thyroid hormone and reverses the weight loss associated with hyperthyroidism. Similarly, inhibition of thyroid hormone receptors in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation, as genetic inhibition of this enzyme in the VMH of euthyroid rats induces feeding-independent weight loss and increases expression of thermogenic markers in BAT. These effects are reversed by pharmacological blockade of the SNS. Thus, thyroid hormone-induced modulation of AMPK activity and lipid metabolism in the hypothalamus is a major regulator of whole-body energy homeostasis.
甲状腺激素对细胞有广泛的影响，但尚不清楚其对中枢神经系统 (CNS) 的影响是否有助于整体能量平衡。在这里，我们证明全身性甲状腺功能亢进或三碘甲状腺原氨酸 (T3) 的中枢给药都会降低下丘脑 AMP 激活蛋白激酶 (AMPK) 的活性，增加交感神经系统 (SNS) 的活性，并上调棕色脂肪组织 (BAT) 的产热标志物。在下丘脑腹内侧核 (VMH) 中抑制脂肪生成途径可防止甲状腺激素介导的 BAT 中枢激活，并逆转与甲状腺功能亢进相关的体重减轻。同样，在 VMH 中抑制甲状腺激素受体也可逆转与甲状腺功能亢进相关的体重减轻。这种调节机制取决于 AMPK 的失活，因为在甲状腺功能正常的大鼠 VMH 中抑制这种酶的遗传可导致与摄食无关的体重减轻，并增加 BAT 中产热标志物的表达。这些作用可通过 SNS 的药理学阻断来逆转。因此，甲状腺激素诱导的下丘脑 AMPK 活性和脂质代谢的调节是全身能量平衡的主要调节剂。
