Yang, XueXueYangZhang, ManlingManlingZhangXie, BingxianBingxianXiePeng, ZishanZishanPengManning, Janet R.Janet R.ManningZimmerman, RaymondRaymondZimmermanWang, QinQinWangAN-CHI WEIKhalifa, MoustafaMoustafaKhalifaReynolds, MichaelMichaelReynoldsJin, JennyJennyJinOm, MatthewMatthewOmZhu, GuangshuoGuangshuoZhuBedja, DjahidaDjahidaBedjaJiang, HongHongJiangJurczak, MichaelMichaelJurczakShiva, SrutiSrutiShivaScott, IainIainScottO'Rourke, BrianBrianO'RourkeKass, David A.David A.KassPaolocci, NazarenoNazarenoPaolocciFeng, NingNingFeng2023-04-242023-04-242023-03-310008-63631755-3245https://scholars.lib.ntu.edu.tw/handle/123456789/630462AIMS: Brain-derived neurotrophic factor (BDNF) is markedly decreased in heart failure patients. Both BDNF and its receptor, tropomyosin-related kinase receptor (TrkB), are expressed in cardiomyocytes; however, the role of myocardial BDNF signalling in cardiac pathophysiology is poorly understood. Here, we investigated the role of BDNF/TrkB signalling in cardiac stress response to exercise and pathological stress. METHODS AND RESULTS: We found that myocardial BDNF expression was increased in mice with swimming exercise but decreased in a mouse heart failure model and human failing hearts. Cardiac-specific TrkB knockout (cTrkB KO) mice displayed a blunted adaptive cardiac response to exercise, with attenuated upregulation of transcription factor networks controlling mitochondrial biogenesis/metabolism, including peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). In response to pathological stress (transaortic constriction, TAC), cTrkB KO mice showed an exacerbated heart failure progression. The downregulation of PGC-1α in cTrkB KO mice exposed to exercise or TAC resulted in decreased cardiac energetics. We further unravelled that BDNF induces PGC-1α upregulation and bioenergetics through a novel signalling pathway, the pleiotropic transcription factor Yin Yang 1. CONCLUSION: Taken together, our findings suggest that myocardial BDNF plays a critical role in regulating cellular energetics in the cardiac stress response.enBDNF | cardiac energetics | heart failure | PGC-1α | YY1[SDGs]SDG3journal article10.1093/cvr/cvac096357040402-s2.0-85151556638WOS:000814800000001https://api.elsevier.com/content/abstract/scopus_id/85151556638