Myocardial brain-derived neurotrophic factor regulates cardiac bioenergetics through the transcription factor Yin Yang 1

Xue Yang, Manling Zhang, Bingxian Xie, Zishan Peng, Janet R. Manning, Raymond Zimmerman, Qin Wang, An Chi Wei, Moustafa Khalifa, Michael Reynolds, Jenny Jin, Matthew Om, Guangshuo Zhu, Djahida Bedja, Hong Jiang, Michael Jurczak, Sruti Shiva, Iain Scott, Brian O'Rourke, David A. KassNazareno Paolocci, Ning Feng

Research output: Contribution to journalArticlepeer-review


Aims 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.

Original languageEnglish (US)
Pages (from-to)571-586
Number of pages16
JournalCardiovascular research
Issue number2
StatePublished - Feb 1 2023


  • BDNF
  • PGC-1α
  • YY1
  • cardiac energetics
  • heart failure

ASJC Scopus subject areas

  • Medicine(all)


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