Oleic Acid Directly Regulates POMC Neuron Excitability in the Hypothalamus
Oleic Acid Directly Regulates POMC Neuron Excitability in the Hypothalamus
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DOI：
10.1152/jn.91294.2008
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发表时间：
2009-05-01
影响因子：
2.5
通讯作者：
Chua, Streamson, Jr.
中科院分区：
文献类型：
--
作者：
Jo, Young-Hwan;Su, Ya;Chua, Streamson, Jr.
引用本文：赵永华，苏莹，Gutierrez-Juarez R, chus Jr.油酸直接调控下丘脑POMC神经元的兴奋性。中国生物医学工程学报（英文版），2009。2009年3月4日首次发表；doi: 10.1152 / jn.91294.2008。哺乳动物的中枢神经系统依靠持续的外部葡萄糖供应来维持其不受干扰的运作。然而，神经元可以很容易地转换使用脂肪酸和酮作为替代燃料。在这里，我们发现油酸（OA）通过抑制atp激活的钾（K-ATP）通道来激活促鸦片黑素皮质素（POMC）神经元。SUR1 KO动物的实验进一步支持了K-ATP通道的参与。使用肉碱棕榈酰基转移酶-1抑制剂抑制β -氧化可阻断oa诱导的去极化。OA的去极化作用是特异性的，因为它不被辛酸模仿。此外，OA不调节针刺相关肽神经元的兴奋性。高脂肪喂养会改变POMC神经元的兴奋性，但不会改变其对OA的反应。因此，POMC神经元中的β -氧化可能介导OA的食欲抑制（厌食）作用。
Jo Y-H, Su Y, Gutierrez-Juarez R, Chua S Jr. Oleic acid directly regulates POMC neuron excitability in the hypothalamus. J Neurophysiol 101: 2305-2316, 2009. First published March 4, 2009; doi:10.1152/jn.91294.2008. The mammalian CNS relies on a constant supply of external glucose for its undisturbed operation. However, neurons can readily switch to using fatty acids and ketones as alternative fuels. Here, we show that oleic acid (OA) excites pro-opiomelanocortin (POMC) neurons by inhibition of ATP-activated potassium (K-ATP) channels. The involvement of K-ATP channels is further supported by experiments in SUR1 KO animals. Inhibition of beta-oxidation using carnitine palmitoyltransferase-1 inhibitors blocks OA-induced depolarization. The depolarizing effect of OA is specific because it is not mimicked by octanoic acid. Furthermore, OA does not regulate the excitability of agouti-related peptide neurons. High-fat feeding alters POMC neuron excitability, but not its response to OA. Thus beta-oxidation in POMC neurons may mediate the appetite-suppressing (anorexigenic) effects of OA.