# Administrative supplement - Feng

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $67,068

## Abstract

ABSTRACT
 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 signaling in cardiac pathophysiology is
poorly understood. During my K08 award tenure, we found that myocardial BDNF expression
was increased in mice with swimming exercise, but decreased in a mouse heart failure model.
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). However, due to the COVID-19 pandemic, the
experiments to assess the functional consequence of suppressed PGC-1α and other metabolic
transcription factors expression were delayed. In the funded extension period, we will test
whether endurance exercise induced cardiac bioenergetic enhancement is attenuated in cTrkB
KO mice by mitochondrial biogenesis assessment and mitochondrial respiratory function
measurement using Oroboros Respirometer. We also found, in response to pathological stress
(transaortic constriction, TAC), cTrkB KO mice showed an exacerbated heart failure progression.
The expression of PGC-1α and other metabolic transcription factors were downregulated in
cTrkB KO mice exposed to TAC. Consistent with this, mitochondrial DNA copy number and
mitochondrial protein abundance was markedly decreased in cTrkB KO mice, resulting in
decreased mitochondrial respiratory function. We further unraveled that BDNF induces PGC-1α
upregulation and bioenergetics through a novel signaling pathway, the pleiotropic transcription
factor Yin Yang 1 (YY1). However, the molecular mechanism of the activation of YY1 by
BDNF/TrkB signaling is unclear. In the extension period, we will further delineate the underlying
mechanisms of the BDNF induced YY1 activation.

## Key facts

- **NIH application ID:** 10393096
- **Project number:** 3K08HL130604-06S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Ning Feng
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $67,068
- **Award type:** 3
- **Project period:** 2018-01-15 → 2022-03-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10393096

## Citation

> US National Institutes of Health, RePORTER application 10393096, Administrative supplement - Feng (3K08HL130604-06S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10393096. Licensed CC0.

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