ArticleCell reports2024
Hepatocyte Period 1 dictates oxidative substrate selection independent of the core circadian clock.
Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Reciprocal oscillation and host-microbial communication in liver metabolic control.Gut microbes · 2025Review
- Dimorphic regulation of time-restricted feeding effects by hepatocyte Period 1.Molecular metabolism · 2025Article
- Targeting hepatocyte-specific SLC2A8 blocks hepatic steatosis and dissociates TCA cycle flux inhibition from glutamine anaplerosis.Hepatology communications · 2025Article
- Daytime-Dependent Effects of Thiamine on the Thiamine Pool and Pyruvate Dehydrogenase Regulation in the Brain and Heart.International journal of molecular sciences · 2025Article
- Research progress on the role and mechanism of circadian clock geneFrontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Organisms integrate circadian and metabolic signals to optimize substrate selection to survive starvation, yet precisely how this occurs is unclear. Here, we show that hepatocyte Period 1 (Per1) is selectively induced during fasting, and mice lacking hepatocyte Per1 fail to initiate autophagic flux, ketogenesis, and lipid accumulation. Transcriptomic analyses show failed induction of the fasting hepatokine Fgf21 in Per1-deficient mice, and single-nucleus multiome sequencing defines a putative responding hepatocyte subpopulation that fails to induce the chromatin accessibility near the Fgf21 locus. In vivo isotopic tracing and indirect calorimetry demonstrate that hepatocyte Per1-deficient mice fail to transit from oxidation of glucose to fat, which is completely reversible by exogenous FGF21 or by inhibiting pyruvate dehydrogenase. Strikingly, disturbing other core circadian genes does not perturb Per1 induction during fasting. We thus describe Per1 as an important mechanism by which hepatocytes integrate internal circadian rhythm and external nutrition signals to facilitate proper fuel utilization.
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