Role of Exendin-4 in Brain Insulin Resistance, Mitochondrial Function, and Neurite Outgrowth in Neurons under Palmitic Acid-Induced Oxidative Stress.
Danbi JoGwangho YoonJuhyun SongPublished in: Antioxidants (Basel, Switzerland) (2021)
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.
Keyphrases
- insulin resistance
- induced apoptosis
- cerebral ischemia
- type diabetes
- oxidative stress
- cognitive decline
- endoplasmic reticulum stress
- metabolic syndrome
- adipose tissue
- resting state
- reactive oxygen species
- spinal cord
- white matter
- diabetic rats
- weight loss
- subarachnoid hemorrhage
- high fat diet
- fatty acid
- cell cycle arrest
- traumatic brain injury
- mild cognitive impairment
- high fat diet induced
- skeletal muscle
- cardiovascular disease
- machine learning
- cell death
- dna damage
- electronic health record
- functional connectivity
- brain injury
- physical activity
- glycemic control
- high resolution
- weight gain
- inflammatory response
- body mass index
- lps induced
- photodynamic therapy
- big data
- endothelial cells
- replacement therapy
- drug induced
- cell proliferation
- solid state