Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model

Autor: Atsushi Morio, Rie Tsutsumi, Shiho Satomi, Takashi Kondo, Hirotsugu Miyoshi, Takahiro Kato, Masashi Kuroda, Tadahiro Kitamura, Kenta Hara, Noboru Saeki, Hiroshi Sakaue, Yasuo M. Tsutsumi
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Diabetology & Metabolic Syndrome, Vol 13, Iss 1, Pp 1-8 (2021)
Druh dokumentu: article
ISSN: 1758-5996
DOI: 10.1186/s13098-021-00755-z
Popis: Abstract 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
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