ArticleNucleic acids research2025
Repeated fasting events sensitize enhancers, transcription factor activity and gene expression to support augmented ketogenesis.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Every-Other-Day Fasting Prehabilitation Attenuates Secondary Injury Following Spinal Cord Injury and Is Associated with Stage-Dependent SREBP1-Related Metabolic-Immune Remodeling.Molecular neurobiology · 2026Article
- Endocrine regulation of the hepatic fasting response: cues, cooperation and consequences.Nature reviews. Endocrinology · 2026Review
- Article
- Peroxisome proliferator‑activated receptor α regulates acesulfame‑K‑induced NAFLD via hepatic PLCβ: Foe and friend.International journal of molecular medicine · 2026Article
- Intermittent Fasting Enhances Genome Integrity and Cytoprotective Pathways via (BHB) β-Hydroxybutyrate Signaling and Chromatin Remodeling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- NF-κB restrains nutrient-dependent transcription programs through chromatin modulation in Drosophila.Nucleic acids research · 2026Article
- Beneficial Outcome Pathways: A New Mechanistic Framework to Map the Health Effects of Fasting in Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of nutrition and metabolism · 2026Review
- Enhancer binding as a KEysTONE of fasting response.Trends in endocrinology and metabolism: TEM · 2025Article
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Authors and funding
15 authors.
Funding
Abstract
Mammals withstand frequent and prolonged fasting periods due to hepatic production of glucose and ketone bodies. Because the fasting response is transcriptionally regulated, we asked whether enhancer dynamics impose a transcriptional program during recurrent fasting and whether this generates effects distinct from a single fasting bout. We found that mice undergoing alternate-day fasting (ADF) respond profoundly differently to a following fasting bout compared to mice first experiencing fasting. Hundreds of genes enabling ketogenesis are 'sensitized' (i.e. induced more strongly by fasting following ADF). Liver enhancers regulating these genes are also sensitized and harbor increased binding of PPARα, the main ketogenic transcription factor. ADF leads to augmented ketogenesis compared to a single fasting bout in wild-type, but not hepatocyte-specific PPARα-deficient mice. Thus, we found that past fasting events are 'remembered' in hepatocytes, sensitizing their enhancers to the next fasting bout and augment ketogenesis. Our findings shed light on transcriptional regulation mediating adaptation to repeated signals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.