Glucocorticoid chrono-pharmacology unveils novel targets for the cardiomyocyte-specific GR-KLF15 axis in cardiac glucose metabolism.

ABSTRACT: Circadian time-of-intake gates the cardioprotective effects of glucocorticoid administration in both healthy and infarcted hearts. The cardiomyocyte-specific glucocorticoid receptor (GR) and its co-factor, Krüppel-like factor (Klf15), play critical roles in maintaining normal heart function in the long-term and serve as pleiotropic regulators of cardiac metabolism. Despite this understanding, the cardiomyocyte-autonomous metabolic targets influenced by the concerted epigenetic action of GR-Klf15 axis remain undefined. Here, we demonstrate the critical roles of the cardiomyocyte-specific GR and Klf15 in orchestrating a circadian-dependent glucose oxidation program within the heart. Combining integrated transcriptomics and epigenomics with cardiomyocyte-specific inducible ablation of GR or K

SUBMITTER: Durumutla HB 

PROVIDER: S-EPMC10769285 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature