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Enhancer binding as a KEysTONE of fasting response.

Nathaniel F Henneman1, Ganna Panasyuk1

  • 1Institut Necker-Enfants Malades, INSERM U1151/CNRS UMR 8253; Paris, 75015, France; Université de Paris Cité; Paris, 75006, France.

Trends in Endocrinology and Metabolism: TEM
|March 8, 2025
PubMed
Summary

Fasting benefits health and longevity. New research shows peroxisome proliferator-activated receptor alpha (PPARα) enhancer priming is key to ketone production during fasting, clarifying metabolic benefits.

Keywords:
PPARα transcription factoralternate-day fastingenhancersketogenesistranscriptional remodeling

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Area of Science:

  • Metabolic regulation
  • Molecular biology
  • Aging research

Background:

  • Fasting is a conserved metabolic stress promoting healthspan and lifespan.
  • Ketone bodies are crucial fuels during fasting periods.
  • The transcriptional regulation of ketone production is not fully understood.

Purpose of the Study:

  • To elucidate the transcriptional mechanisms governing ketone production during fasting.
  • To investigate the role of peroxisome proliferator-activated receptor alpha (PPARα) in fasting adaptation.

Main Methods:

  • The study by Korenfeld et al. investigated enhancer priming in the context of fasting.
  • Analysis focused on the transcriptional regulation of genes involved in ketone body synthesis.

Main Results:

  • Peroxisome proliferator-activated receptor alpha (PPARα)-dependent enhancer priming was identified as a critical mechanism.
  • This priming facilitates efficient ketone production in response to fasting.
  • Findings advance the understanding of metabolic adaptations during alternate-day fasting (ADF).

Conclusions:

  • PPARα-dependent enhancer priming is a keystone mechanism for ketone production during fasting.
  • This discovery provides new insights into the metabolic benefits of fasting interventions like ADF.
  • Understanding these pathways may lead to strategies for enhancing healthspan and lifespan.