Key result
Asprosin exacerbates cardiac hypertrophy by stabilizing PFKP, driving aberrant glycolysis and impairing mitochondrial ATP production.
Why the study?
Metabolic reprogramming toward enhanced glycolysis is a hallmark of pathological cardiac hypertrophy, but the underlying regulatory mechanisms remain unclear.
The YY1-asprosin-PFKP-PDK4-PDH axis drives metabolic reprogramming toward glycolysis in pathological cardiac hypertrophy, highlighting plasma asprosin as a potential biomarker and therapeutic target.
Should not yet change clinical practice; hypothesis-generating for plasma asprosin as biomarker and target in HF.
In hypertrophic and failing hearts, fuel metabolism is reprogrammed toward enhanced glycolysis. Here, we identify asprosin, an adipokine, as a critical regulator of this process in pathological cardiac hypertrophy. In patients, circulating asprosin levels correlate with NT-proBNP and EF. Cardiomyocyte-specific asprosin overexpression aggravates hypertrophy, abnormal glycolysis, and impairs mitochondrial ATP production in male mice, whereas its deficiency confers protection against TAC- or Ang II-induced remodeling in male/female mice. Mechanistically, asprosin binds PFKP and inhibits the K48-linked ubiquitination by DTX3L, thereby stabilizing PFKP and driving aberrant glycolysis, PDK4 induction, PDH inhibition, and impaired respiration. Genetic knockdown of PFKP mitigates hypertrophy and fibrosis in male mice, whereas PFKP overexpression abolishes the protective effects conferred by FBN1 knockdown. Moreover, YY1 is identified as a transcriptional activator of asprosin in the hypertrophic hearts of male mice. Here we show that the YY1–asprosin–PFKP–PDK4–PDH axis underlies metabolic remodeling, and we highlight plasma asprosin as a potential early biomarker and therapeutic target for cardiac dysfunction. Metabolic reprogramming toward glycolysis is a hallmark of pathological cardiac hypertrophy, but the regulatory mechanisms remain unclear. Here the authors show that the adipokine, asprosin, drives hypertrophic metabolic remodeling by stabilizing PFKP and activating a YY1–asprosin–PFKP–PDK4–PDH axis.
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Tong et al. (2026) studied Pathological cardiac hypertrophy. Asprosin overexpression and knockdown vs. Control (AAV9-NC / shNC) was evaluated on Cardiac hypertrophy and glycolytic metabolism. Asprosin exacerbates pathological cardiac hypertrophy by stabilizing PFKP, which drives aberrant glycolysis and impairs mitochondrial ATP production.
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