Exenatide Attenuates Obesity-Induced Mitochondrial Dysfunction by Activating SIRT1 in Renal Tubular Cells
| العنوان: | Exenatide Attenuates Obesity-Induced Mitochondrial Dysfunction by Activating SIRT1 in Renal Tubular Cells |
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| المؤلفون: | Ming Yang, Wei He, Yao Wang, Xiaoxue Mei, Wei Wei, Ying Wang |
| المصدر: | Frontiers in Endocrinology, Vol 12 (2021) Frontiers in Endocrinology |
| بيانات النشر: | Frontiers Media SA, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Blood Glucose, Male, Mitochondrial ROS, Agonist, Simvastatin, obesity, medicine.drug_class, Endocrinology, Diabetes and Metabolism, glucagon-like peptide-1 receptor agonist, Palmitates, Down-Regulation, Apoptosis, In Vitro Techniques, Pharmacology, Diet, High-Fat, renal tubular cells, Diseases of the endocrine glands. Clinical endocrinology, Cell Line, Mice, Endocrinology, SIRT1, Sirtuin 1, Downregulation and upregulation, mitochondrial dysfunction, medicine, Animals, Humans, Hypoglycemic Agents, Original Research, Membrane Potential, Mitochondrial, chemistry.chemical_classification, Reactive oxygen species, Chemistry, Body Weight, RC648-665, Mitochondria, Mice, Inbred C57BL, Kidney Tubules, Lipotoxicity, Exenatide, lipids (amino acids, peptides, and proteins), Reactive Oxygen Species, hormones, hormone substitutes, and hormone antagonists, medicine.drug |
| الوصف: | Saturated free fatty acid (FFA)-induced lipotoxicity plays an important role in obesity-induced kidney injury. Exenatide, a Glucagon-like peptide-1 receptor agonist(GLP-1RA), protects against high-fat diet (HFD)-induced kidney injury. The precise mechanism needs to be further explored. This study investigated whether exenatide protects against FFA-induced tubular epithelial cells (TECs) lipotoxicity and elucidated its underlying mechanisms. Here, we show that exenatide treatment reversed HFD induced TECs injuries, including TECs apoptosis and SIRT1 downregulation. The efficacy of exenatide was better than simvastatin. In palmitate (PA)-stimulated HK2 cells, exenatide treatment reversed the downregulation of SIRT1 and prevented an increase in reactive oxygen species (ROS) production, a decrease in mitochondrial membrane potential, and mitochondrial apoptosis. The renal-protective effects of exenatide on the generation of mitochondrial ROS and mitochondrial apoptosis were blocked by inhibiting SIRT1 activation. Collectively, these findings show that exenatide was superior to simvastatin in the treatment of obesity-TECs injuries, the mechanism is partially through SIRT1 restoration, which directly reverses mitochondrial dysfunction and apoptosis. |
| تدمد: | 1664-2392 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4a689ce0396d189791634403d6417c3Test https://doi.org/10.3389/fendo.2021.622737Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b4a689ce0396d189791634403d6417c3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16642392 |
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