Palmitic acid stimulates energy metabolism and inhibits insulin/PI3K/AKT signaling in differentiated human neuroblastoma cells: The role of mTOR activation and mitochondrial ROS production
Palmitic acid stimulates energy metabolism and inhibits insulin/PI3K/AKT signaling in differentiated human neuroblastoma cells: The role of mTOR activation and mitochondrial ROS production
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DOI：
10.1016/j.neuint.2017.09.008
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发表时间：
2017-11-01
影响因子：
4.2
通讯作者：
Arias, Clorinda
中科院分区：
文献类型：
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作者：
Calvo-Ochoa, Erika;Sanchez-Alegria, Karina;Arias, Clorinda
饱和脂质的高消耗在很大程度上与代谢疾病患病率的增加有关。特别是，饱和脂肪酸如棕榈酸（PA）与外周组织胰岛素抵抗的发展有关。然而，神经元如何因脂质超载而产生胰岛素抵抗尚不完全清楚。在这里，我们使用培养的大鼠皮质神经元和分化的人神经母细胞瘤细胞来证明 PA 阻断胰岛素诱导的代谢激活，抑制胰岛素/PI3K/Akt 通路的激活并激活 Akt 下游的 mTOR 激酶。尽管脂肪酸通常不被神经细胞用作重要的燃料来源，但我们还发现短期神经元暴露于 PA 会降低 NAD/NADH 比率，表明 PA 改变神经元能量平衡。最后，用 mitoTEMPO 抑制线粒体 ROS 的产生，可以防止 PA 对胰岛素信号传导的有害影响。这项工作为饱和脂肪酸诱导的胰岛素抵抗背后的机制及其对神经元细胞的代谢影响提供了新的证据。 (C) 2017 Elsevier Ltd. 保留所有权利。
The high consumption of saturated lipids has been largely associated with the increasing prevalence of metabolic diseases. In particular, saturated fatty acids such as palmitic acid (PA) have been implicated in the development of insulin resistance in peripheral tissues. However, how neurons develop insulin resistance in response to lipid overload is not fully understood. Here, we used cultured rat cortical neurons and differentiated human neuroblastoma cells to demonstrate that PA blocks insulin-induced metabolic activation, inhibits the activation of the insulin/PI3K/Akt pathway and activates mTOR kinase downstream of Akt. Despite the fact that fatty acids are not normally used as a significant source of fuel by neural cells, we also found that short-term neuronal exposure to PA reduces the NAD/NADH ratio, indicating that PA modifies the neuronal energy balance. Finally, inhibiting mitochondrial ROS production with mitoTEMPO prevented the deleterious effect of PA on insulin signaling. This work provides novel evidence of the mechanisms behind saturated fatty acid-induced insulin resistance and its metabolic consequences on neuronal cells. (C) 2017 Elsevier Ltd. All rights reserved.