Glucagon like peptide 1 (GLP-1) is an incretin hormone produced by the gut and brain, and is currently being used as a therapeutic drug for type 2 diabetes and obesity, suggesting that it regulates abnormal appetite patterns, and ameliorates impaired glucose metabolism. Many researchers have demonstrated that GLP-1 agonists and GLP-1 receptor agonists exert neuroprotective effects against brain damage. Palmitic acid (PA) is a saturated fatty acid, and increases the risk of neuroinflammation, lipotoxicity, impaired glucose metabolism, and cognitive decline. In this study, we investigated whether or not Exentin-4 (Ex-4; GLP-1 agonist) inhibits higher production of reactive oxygen species (ROS) in an SH-SY5Y neuronal cell line under PA-induced apoptosis conditions. Moreover, pre-treatment with Ex-4 in SH-SY5Y neuronal cells prevents neural apoptosis and mitochondrial dysfunction through several cellular signal pathways. In addition, insulin sensitivity in neurons is improved by Ex-4 treatment under PA-induced insulin resistance. Additionally, our imaging data showed that neuronal morphology is improved by EX-4 treatment, in spite of PA-induced neuronal damage. Furthermore, we identified that Ex-4 inhibits neuronal damage and enhanced neural complexity, such as neurite length, secondary branches, and number of neurites from soma in PA-treated SH-SY5Y. We observed that Ex-4 significantly increases neural complexity, dendritic spine morphogenesis, and development in PA treated primary cortical neurons. Hence, we suggest that GLP-1 administration may be a crucial therapeutic solution for improving neuropathology in the obese brain.

中文翻译：

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Exendin-4在棕榈酸诱导的氧化应激下神经元中脑胰岛素抵抗，线粒体功能和神经突生长的作用

胰高血糖素样肽1（GLP-1）是由肠道和大脑产生的肠降血糖素激素，目前被用作2型糖尿病和肥胖症的治疗药物，表明它调节异常的食欲模式，并改善受损的葡萄糖代谢。许多研究人员已经证明，GLP-1激动剂和GLP-1受体激动剂对脑部损伤具​​有神经保护作用。棕榈酸（PA）是一种饱和脂肪酸，会增加神经炎症，脂毒性，葡萄糖代谢受损和认知能力下降的风险。在这项研究中，我们调查了Exentin-4（Ex-4； GLP-1激动剂）是否在PA诱导的凋亡条件下抑制SH-SY5Y神经元细胞系中较高的活性氧（ROS）生成。此外，在SH-SY5Y神经元细胞中用Ex-4进行预处理可通过几种细胞信号途径防止神经细胞凋亡和线粒体功能障碍。此外，在PA诱导的胰岛素抵抗下，通过Ex-4处理可改善神经元中的胰岛素敏感性。此外，我们的影像数据显示，尽管PA诱发了神经元损害，但EX-4处理可改善神经元形态。此外，我们发现Ex-4可以抑制PA处理的SH-SY5Y中神经元的损伤并增强神经的复杂性，例如神经突的长度，次级分支和来自躯体的神经突的数量。我们观察到Ex-4显着增加了PA治疗的原代皮层神经元的神经复杂性，树突棘形态发生和发育。因此，