Apolipoprotein E reduces food intake via PI3K/Akt signaling pathway in the hypothalamus.
Apolipoprotein E reduces food intake via PI3K/Akt signaling pathway in the hypothalamus.
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DOI：
10.1016/j.physbeh.2011.04.018
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发表时间：
2011-11-30
影响因子：
2.9
通讯作者：
Liu, Min
中科院分区：
文献类型：
--
作者：
Shen, Ling;Wang, David Q-H.;Tso, Patrick;Jandacek, Ronald J.;Woods, Stephen C.;Liu, Min
载脂蛋白E（apoE）是一种饱食因子。虽然中央apoE管理减少食物摄入量，特定的细胞内信号转导机制激活apoE仍然在很大程度上未知。使用原代培养的下丘脑神经元，我们证明了apoE处理（50 nM）引起磷脂酰肌醇-3-激酶（PI 3 K）/Akt信号级联反应的快速激活。具体而言，apoE诱导Akt的磷酸化，在30 min达到峰值，并且在用LY 294002（50 μM）（PI 3 K信号通路抑制剂）预处理后，Akt的磷酸化水平显著减弱。为了确定apoE减少食物摄入的能力是否需要apoE激活PI 3 K，在注射厌食剂量的apoE之前将LY 294002（1 nmol）输注到第三脑室中。与我们以前的报告一致，apoE（4 μg）与生理盐水相比，在禁食4小时的大鼠中表现出显著的摄食减少。用LY 294002预处理显著减弱了外源性apoE诱导饱食的效力，而相同剂量的PI 3 K抑制剂本身仅引起轻微的非显著性摄食减少。这些结果表明，PI 3 K/Akt通路的激活是apoE对食物摄入的急性效应所必需的。
Apolipoprotein E (apoE) is a satiation factor. While central apoE administration reduces food intake, the specific intracellular signaling mechanisms activated by apoE remain largely unknown. Using primary cultured hypothalamic neurons, we demonstrated that apoE treatment (50 nM) elicited rapid activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling cascade. Specifically, apoE induced the phosphorylation of Akt, peaking at 30 min, and the increased phosphorylation of Akt was significantly attenuated after pretreatment with LY294002 (50 μM), an inhibitor of the PI3K signaling pathway. To determine whether the activation of PI3K by apoE is required for the ability of apoE to reduce food intake, LY294002 (1 nmol) was infused into the 3rd-cerebral ventricle before injection of an anorectic dose of apoE. Consistent with our previous report, apoE (4 μg) exerted significant reduction of food intake in the 4-h fasted rats, compared with saline. Pretreatment with LY294002 significantly attenuated the potency of exogenous apoE to induce satiation, while the same dose of PI3K inhibitor by itself caused only a slight non-significant decrease of food intake. These results indicate that the activation of the PI3K/Akt pathway is necessary for the acute effects of apoE on food intake.
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作者：
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影响因子：
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