Role of Exendin-4 in Brain Insulin Resistance, Mitochondrial Function, and Neurite Outgrowth in Neurons under Palmitic Acid-Induced Oxidative Stress
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 demonst...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/1/78 |
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| author | Danbi Jo Gwangho Yoon Juhyun Song |
| author_facet | Danbi Jo Gwangho Yoon Juhyun Song |
| author_sort | Danbi Jo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:29:25Z |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T05:29:25Z |
| publishDate | 2021-01-01 |
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| series | Antioxidants |
| spelling | doaj.art-92e17deac21a4e459f91f1711b0ca8e72023-12-03T12:33:38ZengMDPI AGAntioxidants2076-39212021-01-011017810.3390/antiox10010078Role of Exendin-4 in Brain Insulin Resistance, Mitochondrial Function, and Neurite Outgrowth in Neurons under Palmitic Acid-Induced Oxidative StressDanbi Jo0Gwangho Yoon1Juhyun Song2Department of Anatomy, Chonnam National University Medical School, Hwasun 58128, KoreaDepartment of Anatomy, Chonnam National University Medical School, Hwasun 58128, KoreaDepartment of Anatomy, Chonnam National University Medical School, Hwasun 58128, KoreaGlucagon 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.https://www.mdpi.com/2076-3921/10/1/78exendin-4 (Ex-4)glucagon like petide-1 (GLP-1)neuronal structureobesitypalmitic acid (PA) |
| spellingShingle | Danbi Jo Gwangho Yoon Juhyun Song Role of Exendin-4 in Brain Insulin Resistance, Mitochondrial Function, and Neurite Outgrowth in Neurons under Palmitic Acid-Induced Oxidative Stress Antioxidants exendin-4 (Ex-4) glucagon like petide-1 (GLP-1) neuronal structure obesity palmitic acid (PA) |
| title | Role of Exendin-4 in Brain Insulin Resistance, Mitochondrial Function, and Neurite Outgrowth in Neurons under Palmitic Acid-Induced Oxidative Stress |
| title_full | Role of Exendin-4 in Brain Insulin Resistance, Mitochondrial Function, and Neurite Outgrowth in Neurons under Palmitic Acid-Induced Oxidative Stress |
| title_fullStr | Role of Exendin-4 in Brain Insulin Resistance, Mitochondrial Function, and Neurite Outgrowth in Neurons under Palmitic Acid-Induced Oxidative Stress |
| title_full_unstemmed | Role of Exendin-4 in Brain Insulin Resistance, Mitochondrial Function, and Neurite Outgrowth in Neurons under Palmitic Acid-Induced Oxidative Stress |
| title_short | Role of Exendin-4 in Brain Insulin Resistance, Mitochondrial Function, and Neurite Outgrowth in Neurons under Palmitic Acid-Induced Oxidative Stress |
| title_sort | role of exendin 4 in brain insulin resistance mitochondrial function and neurite outgrowth in neurons under palmitic acid induced oxidative stress |
| topic | exendin-4 (Ex-4) glucagon like petide-1 (GLP-1) neuronal structure obesity palmitic acid (PA) |
| url | https://www.mdpi.com/2076-3921/10/1/78 |
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