Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model
| Autor: | Takahiro Kato, Hiroshi Sakaue, Tadahiro Kitamura, Rie Tsutsumi, Takashi Kondo, Masashi Kuroda, Yasuo M. Tsutsumi, Shiho Satomi, Atsushi Morio, Hirotsugu Miyoshi, Kenta Hara, Noboru Saeki |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
RC620-627 Endocrinology Diabetes and Metabolism Mitochondrion Leucine In vivo Internal medicine Internal Medicine Medicine Nutritional diseases. Deficiency diseases PI3K/AKT/mTOR pathway chemistry.chemical_classification Reactive oxygen species business.industry Research medicine.disease Myocardial ischemia/reperfusion injury High-fat diet Endocrinology mitochondrial fusion chemistry Ischemic preconditioning Cardioprotective business Reperfusion injury |
| Zdroj: | Diabetology & Metabolic Syndrome, Vol 13, Iss 1, Pp 1-8 (2021) Diabetology & Metabolic Syndrome |
| ISSN: | 1758-5996 |
| DOI: | 10.1186/s13098-021-00755-z |
| Popis: | Background Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart. Methods In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/−, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment. Results Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p +/− mice. Additionally, Leu increased the percentage of fused mitochondria and the mitochondrial volume, and decreased the number of mitochondria per cell in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment significantly reduced infarct size (41.0% ± 1.1% vs. 51.0% ± 1.4%, n = 7, p +/− mice. Conclusions Leu treatment improved the damage caused by myocardial I/R injury by promoting mTOR activity and mitochondrial fusion on prediabetic hearts in mice. |
| Databáze: | OpenAIRE |
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