Heart failure & cardiomyopathies
Insulin Resistance Compromises the Pentose Phosphate Pathway and Impairs Left Ventricular Assist Device–Mediated Myocardial Recovery in Obese Patients With Heart Failure
Authors' conclusion
In failing hearts, mechanical unloading leads to activation of insulin signaling, resulting in increased glucose uptake and enhanced pentose phosphate pathway flux to protect cardiomyocytes against oxidative stress. However, this cardioprotective effect is attenuated by obesity-induced insulin resistance.
Study context
- Population
- Patients with heart failure (HF) receiving LVAD support; mouse model of LVAD-mediated cardiac unloading (HF and obese HF mice)
Methodological detailsclinical cohort and mouse model of heterotopic cervical heart transplantation, single-nucleus RNA sequencing, stable-isotope tracing metabolomics, in vitro cyclic stretch assays
- Clinical cohort and mouse model of heterotopic cervical heart transplantation
- Single-nucleus RNA sequencing
- Stable-isotope tracing metabolomics
- In vitro cyclic stretch assays
Main finding
As reported in the abstract
- HF patients with higher BMI (≥28.0) and greater insulin resistance tended to have poorer LVAD-mediated myocardial recovery
- Mechanical unloading activated myocardial insulin signaling and increased glucose uptake
- Glucose taken up by unloaded hearts preferentially shunted into the pentose phosphate pathway
- Reduced mechanical stress attenuated Hippo pathway activation in cardiomyocytes, facilitating insulin signaling and enhancing pentose phosphate pathway flux
- In unloaded hearts from HF mice, increased pentose phosphate pathway flux could reduce oxidative stress and exert cardioprotective effects
- Benefits blunted by insulin resistance in obese mice; insulin sensitizers alleviated insulin resistance and restored unloading-mediated cardioprotection
Original publication
Insulin Resistance Compromises the Pentose Phosphate Pathway and Impairs Left Ventricular Assist Device–Mediated Myocardial Recovery in Obese Patients With Heart Failure. Circulation. Published 6 February 2026. doi:10.
Summarised from the published abstract; every number is checked against it