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

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Leucine High-fat diet Myocardial ischemia/reperfusion injury Cardioprotective Nutritional diseases. Deficiency diseases RC620-627
Acceso en línea:	https://doaj.org/article/13539f8798bd470098c79f5c743f524b
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spelling	oai:doaj.org-article:13539f8798bd470098c79f5c743f524b2021-11-21T12:40:18ZLeucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model10.1186/s13098-021-00755-z1758-5996https://doaj.org/article/13539f8798bd470098c79f5c743f524b2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13098-021-00755-zhttps://doaj.org/toc/1758-5996Abstract 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 < 0.05), whereas Rap-treated mice did not show the protective effects of Leu. This preconditioning effect of Leu was attenuated in mTOR+/− 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 < 0.05), which was not induced by ischemic preconditioning, and this effect was inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and mitochondrial fusion with decreased reactive oxygen species production with Leu treatment in HFD-induced obese mice, but not in mTOR+/− 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.Atsushi MorioRie TsutsumiShiho SatomiTakashi KondoHirotsugu MiyoshiTakahiro KatoMasashi KurodaTadahiro KitamuraKenta HaraNoboru SaekiHiroshi SakaueYasuo M. TsutsumiBMCarticleLeucineHigh-fat dietMyocardial ischemia/reperfusion injuryCardioprotectiveNutritional diseases. Deficiency diseasesRC620-627ENDiabetology & Metabolic Syndrome, Vol 13, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Leucine High-fat diet Myocardial ischemia/reperfusion injury Cardioprotective Nutritional diseases. Deficiency diseases RC620-627
spellingShingle	Leucine High-fat diet Myocardial ischemia/reperfusion injury Cardioprotective Nutritional diseases. Deficiency diseases RC620-627 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 Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model
description	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 < 0.05), whereas Rap-treated mice did not show the protective effects of Leu. This preconditioning effect of Leu was attenuated in mTOR+/− 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 < 0.05), which was not induced by ischemic preconditioning, and this effect was inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and mitochondrial fusion with decreased reactive oxygen species production with Leu treatment in HFD-induced obese mice, but not in mTOR+/− 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.
format	article
author	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
author_facet	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
author_sort	Atsushi Morio
title	Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model
title_short	Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model
title_full	Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model
title_fullStr	Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model
title_full_unstemmed	Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model
title_sort	leucine imparts cardioprotective effects by enhancing mtor activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model
publisher	BMC
publishDate	2021
url	https://doaj.org/article/13539f8798bd470098c79f5c743f524b
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Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model

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