YY1/Asprosin/PFKP axis regulates glycolytic metabolic and exacerbates pathological cardiac hypertrophy - PubMed
18 hours ago
- #cardiac hypertrophy
- #metabolic reprogramming
- #asprosin
- The study identifies asprosin, an adipokine, as a key regulator of enhanced glycolysis in pathological cardiac hypertrophy, with circulating levels correlating with NT-proBNP and EF in patients.
- Overexpression of asprosin in cardiomyocytes worsens hypertrophy, glycolysis, and mitochondrial ATP production in male mice, while deficiency protects against TAC- or Ang II-induced remodeling in both male and female mice.
- Mechanistically, asprosin binds to PFKP, inhibiting its ubiquitination by DTX3L, stabilizing PFKP, and driving aberrant glycolysis, PDK4 induction, PDH inhibition, and impaired respiration.
- Genetic knockdown of PFKP reduces hypertrophy and fibrosis in male mice, and PFKP overexpression negates the protective effects of FBN1 knockdown, linking PFKP to disease progression.
- YY1 is identified as a transcriptional activator of asprosin in hypertrophic hearts of male mice, forming a YY1-asprosin-PFKP-PDK4-PDH axis underlying metabolic remodeling.
- The findings highlight plasma asprosin as a potential early biomarker and therapeutic target for cardiac dysfunction, with implications for metabolic regulation in heart failure.