Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance.
Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance.
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作者：
甲状腺激素具有广泛的细胞效应；然而，目前尚不清楚它们对中枢神经系统(CNS)的影响是否有助于全球能量平衡。在这里，我们证明了无论是全身甲亢还是中枢注射三碘甲腺原氨酸(T3)都降低了下丘脑AMP激活的蛋白激酶(AMPK)的活性，增加了交感神经系统(SNS)的活性，并上调了棕色脂肪组织(BAT)中的生热标志物。抑制下丘脑腹内侧核(VMH)的造脂途径可阻止中枢神经系统介导的甲状腺激素激活BAT，并逆转与甲状腺功能亢进相关的体重减轻。类似地，抑制VMH中的甲状腺激素受体(TRs)可以逆转与甲状腺功能亢进相关的体重减轻。这种调节机制依赖于AMPK的失活，因为在正常甲状腺大鼠的VMH中，该酶的遗传消融导致了摄食非依赖性的体重减轻，并增加了BAT中产热标志物的表达。这些效应被SNS的药理阻断所逆转。因此，甲状腺激素对下丘脑AMPK活性和脂质代谢的调节是能量平衡的重要调节因素。
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 (TRs) in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation as genetic ablation 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 an important regulator of energy homeostasis.
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DOI：
10.1016/0005-2760(83)90284-9
发表时间：
1983-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
GNONI, GV;LANDRISCINA, C;QUAGLIARIELLO, E
通讯作者：
QUAGLIARIELLO, E
影响因子：
3.3
作者：
Irrcher, Isabella;Walkinshaw, Donald R.;Hood, David A.
通讯作者：
Hood, David A.
影响因子：
5.8
作者：
BEYLOT, M;MARTIN, C;MORNEX, R
通讯作者：
MORNEX, R
影响因子：
4.8
作者：
Lage, Ricardo;Vazquez, Maria J.;Lopez, Miguel
通讯作者：
Lopez, Miguel
影响因子：
15.9
作者：
Chakravarthy, Manu V.;Zhu, Yimin;Semenkovich, Clay F.
通讯作者：
Semenkovich, Clay F.