Enhancer binding as a KEysTONE of fasting response

Fasting is a recurrent daily energy stress that benefits healthspan and lifespan. While ketones fuel fasting in vertebrates, the underlying transcriptional mechanism remains incompletely understood. Recently, Korenfeld et al. revealed peroxisome proliferator-activated receptor alpha (PPARα)-dependent enhancer priming as a keystone for ketone production, increasing our understanding of mechanisms underlying metabolic benefits of alternate-day fasting (ADF).