Jo Danbi, Yoon Gwangho, Song Juhyun
Department of Anatomy, Chonnam National University Medical School, Hwasun 58128, Korea.
BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-757, Korea.
Antioxidants (Basel). 2021 Jan 9;10(1):78. doi: 10.3390/antiox10010078.
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.
胰高血糖素样肽1（GLP-1）是一种由肠道和大脑产生的肠促胰岛素激素，目前正被用作治疗2型糖尿病和肥胖症的药物，这表明它能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。在本研究中，我们调查了艾塞那肽-4（Ex-4；GLP-1激动剂）是否能在PA诱导的凋亡条件下抑制SH-SY5Y神经细胞系中活性氧（ROS）的过量产生。此外，在SH-SY5Y神经细胞中用Ex-4预处理可通过多种细胞信号通路防止神经细胞凋亡和线粒体功能障碍。此外，在PA诱导的胰岛素抵抗情况下，Ex-4处理可改善神经元的胰岛素敏感性。另外，我们的成像数据显示，尽管存在PA诱导的神经元损伤，但Ex-4处理可改善神经元形态。此外，我们发现Ex-4可抑制PA处理的SH-SY5Y细胞中的神经元损伤，并增强神经复杂性，如神经突长度、二级分支和从胞体发出的神经突数量。我们观察到Ex-4可显著增加PA处理的原代皮质神经元的神经复杂性、树突棘形态发生和发育。因此，我们认为给予GLP-1可能是改善肥胖大脑神经病理学的关键治疗方案。
