Mitochondrial dynamic modulation exerts cardiometabolic protection in obese insulin-resistant rats
| Autor: | Nipon Chattipakorn, Chayodom Maneechote, Nattayaporn Apaijai, Sasiwan Kerdphoo, Siripong Palee, Thidarat Jaiwongkam, Siriporn C. Chattipakorn |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Cardiac function curve medicine.medical_specialty Cardiotonic Agents Normal diet Apoptosis Mitochondrion Diet High-Fat Mitochondrial Dynamics Mitochondria Heart Insulin resistance Internal medicine Animals Medicine Obesity Rats Wistar Quinazolinones Cardioprotection business.industry General Medicine medicine.disease Endocrinology mitochondrial fusion Mitochondrial fission Insulin Resistance Reactive Oxygen Species business |
| Zdroj: | Clinical Science. 133:2431-2447 |
| ISSN: | 1470-8736 0143-5221 |
| DOI: | 10.1042/cs20190960 |
| Popis: | Obese insulin resistance impairs cardiac mitochondrial dynamics by increasing mitochondrial fission and decreasing mitochondrial fusion, leading to mitochondrial damage, myocardial cell death and cardiac dysfunction. Therefore, inhibiting fission and promoting fusion could provide cardioprotection in this pre-diabetic condition. We investigated the combined effects of the mitochondrial fission inhibitor (Mdivi1) and fusion promoter (M1) on cardiac function in obese insulin-resistant rats. We hypothesized that Mdivi1 and M1 protect heart against obese insulin-resistant condition, but also there will be greater improvement using Mdivi1 and M1 as a combined treatment. Wistar rats (n=56, male) were randomly assigned to a high-fat diet (HFD) and normal diet (ND) fed groups. After feeding with either ND or HFD for 12 weeks, rats in each dietary group were divided into groups to receive either the vehicle, Mdivi1 (1.2 mg/kg, i.p.), M1 (2 mg/kg, i.p.) or combined treatment for 14 days. The cardiac function, cardiac mitochondrial function, metabolic and biochemical parameters were monitored before and after the treatment. HFD rats developed obese insulin resistance which led to impaired dynamics balance and function of mitochondria, increased cardiac cell apoptosis and dysfunction. Although Mdivi1, M1 and combined treatment exerted similar cardiometabolic benefits in HFD rats, the combined therapy showed a greater reduction in mitochondrial reactive oxygen species (ROS). Mitochondrial fission inhibitor and fusion promoter exerted similar levels of cardioprotection in a pre-diabetic condition. |
| Databáze: | OpenAIRE |
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