NRF2 activation in the heart induces glucose metabolic reprogramming and reduces cardiac dysfunction via upregulation of the pentose phosphate pathway.

ABSTRACT:

Aims

The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) is well recognized as a master regulator of antioxidant responses and cytoprotective genes. Previous studies showed that NRF2 enhances the resistance of mouse hearts to chronic haemodynamic overload, at least in part by reducing oxidative stress. Evidence from other tissues suggests that NRF2 may modulate glucose intermediary metabolism but whether NRF2 has such effects in the heart is unclear. Here, we investigate the role of NRF2 in regulating glucose intermediary metabolism and cardiac function during disease stress.

Methods and results

Cardiomyocyte-specific Keap1 knockout (csKeap1KO) mice, deficient in the endogenous inhibitor of NRF2, were used as a novel model of constitutively active NRF2

SUBMITTER: Zoccarato A 

PROVIDER: S-EPMC12012450 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature