Circadian REV-ERBs repress E4bp4 to activate NAMPT-dependent NAD⁺ biosynthesis and sustain cardiac function.

ABSTRACT: The heart is a highly metabolic organ that uses multiple energy sources to meet its demand for ATP production. Diurnal feeding-fasting cycles result in substrate availability fluctuations which, together with increased energetic demand during the active period, impose a need for rhythmic cardiac metabolism. The nuclear receptors REV-ERBα and β are essential repressive components of the molecular circadian clock and major regulators of metabolism. To investigate their role in the heart, here we generated mice with cardiomyocyte (CM)-specific deletion of both Rev-erbs, which died prematurely due to dilated cardiomyopathy. Loss of Rev-erbs markedly downregulated fatty acid oxidation genes prior to overt pathology, which was mediated by induction of the transcriptional repressor

SUBMITTER: Dierickx P 

PROVIDER: S-EPMC8754391 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature