ArticleNature metabolism2025
The hepatic clock synergizes with HIF-1α to regulate nucleotide availability during liver damage repair.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Mitophagy-Competent Cancer-Associated Fibroblasts Fuel Chemoresistance by Rewiring Pyrimidine Metabolism in Pancreatic Cancer.Cancer research · 2026Article
- Proteomic Characterization of Replication Stress and Impaired Antioxidant Defense in Tacrolimus-Induced Chronic Nephrotoxicity.International journal of molecular sciences · 2026Article
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Morphofunctional State of the Liver Under Conditions of Three-Month Dark Deprivation: The Influence of Circadian Disruptions and Melatonin.International journal of molecular sciences · 2026Article
- Polyphenol mediated zinc-oxygen synergistic hydrogel remodels senescent microenvironment for periodontal tissue regeneration.Nature communications · 2026Article
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Circadian clock and cancer.Military Medical Research · 2026Review
- Temporal dynamics and functional annotation of transcriptome rhythmicity in HEK293T cells.PloS one · 2026Article
- Circadian clock genes: Their influence on liver metabolism, disease development and treatment (Review).Molecular medicine reports · 2026Review
- Radix Rehmanniae Praeparata Extract Enhances Liver Regeneration Through AMPK-Driven Metabolic Reprogramming.Nutrients · 2025Article
- Unlocking the therapeutic potential of the STING signaling pathway in anti-tumor treatment.Clinical and experimental medicine · 2025Review
- M6A methyltransferase METTL3 promotes glucose metabolism hub gene expression and induces metabolic dysfunction-associated steatotic liver disease (MASLD).BMC genomics · 2025Article
- Stemness- and hypoxia-based prognostic stratification index reveals G6PD as a regulator of hypoxia-driven stemness in hepatocellular carcinoma.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleotide availability is crucial for DNA replication and repair; however, the coordinating mechanisms in vivo remain unclear. Here, we show that the circadian clock in the liver controls the activity of the pentose phosphate pathway (PPP) to support de novo nucleotide biosynthesis for DNA synthesis demands. We demonstrate that disrupting the hepatic clock by genetic manipulation or mistimed feeding impairs PPP activity in male mice, leading to nucleotide imbalance. Such defects not only elicit DNA replication stress to limit liver regeneration after resection but also allow genotoxin-induced hepatocyte senescence and STING signalling-dependent inflammation. Mechanistically, the molecular clock activator BMAL1 synergizes with hypoxia-inducible factor-1α (HIF-1α) to regulate the transcription of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD), which is enhanced during liver regeneration. Overexpressing G6PD restores the compromised regenerative capacity of the BMAL1- or HIF-1α-deficient liver. Moreover, boosting G6PD expression genetically or through preoperative intermittent fasting potently facilitates liver repair in normal mice. Hence, our findings highlight the physiological importance of the hepatic clock and suggest a promising pro-regenerative strategy.
Indexed as
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39775529What Socratic holds
Registered trials
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