Branched chain amino acids exacerbate myocardial ischemia/reperfusion vulnerability via enhancing GCN2/ATF6/PPAR-α pathway-dependent fatty acid oxidation
Yueyang Li, Zhenyu Xiong, Wenjun Yan, Erhe Gao, Hexiang Cheng, Guiling Wu, Yi Liu, Ling Zhang, Congye Li, Shan Wang, Miaomiao Fan, Huishou Zhao, Fuyang Zhang, Ling Tao
Abstract
: We identify BCAA as an important nutrition regulator of myocardial fatty acid metabolism through transcriptional upregulation of PPAR-α. Chronic accumulation of BCAA, caused by either dietary or genetic factors, renders the heart vulnerable to I/R injury via exacerbating lipid peroxidation toxicity. These data support the notion that BCAA lowering methods might be potentially effective cardioprotective strategies, especially among patients with diseases characterized by elevated levels of BCAA, such as obesity and diabetes.
Topics & Concepts
PeroxisomeChemistryAmino acidIschemiaBeta oxidationMyocardial ischemiaBiochemistryFatty acidInternal medicineCell biologyCardiologyMedicineBiologyGeneCardiac Ischemia and ReperfusionMetabolomics and Mass Spectrometry StudiesAdipose Tissue and Metabolism