ArticleProceedings of the National Academy of Sciences of the United States of America2025
HIF1α mediates circadian regulation of skeletal muscle metabolism and substrate preference in response to time-of-day exercise.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed.
- Circadian biology and exercise: the time to move.Life metabolism · 2026Review
- Adiponectin modulates the diurnal hepatic transcriptome and energy metabolism in male mice.Endocrine connections · 2026Article
- Circadian control of immune homeostasis in cardiovascular health and disease.Frontiers in immunology · 2026Review
- Chrono-combined aerobic-resistance exercises as therapeutic approach to reverse neurodegeneration in rat model: a detailed protocol.Frontiers in aging neuroscience · 2026Article
- HIF1α mediates circadian regulation of skeletal muscle metabolism and substrate preference in response to time-of-day exercise.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exercise, circadian rhythms, and muscle regeneration: a path to healthy aging.Frontiers in neuroscience · 2025Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
The regulation of metabolism in peripheral tissues is intricately linked to circadian rhythms, with hypoxia-inducible factor-1α (HIF1α) implicated in modulating time-of-day-specific exercise responses. To investigate this relationship, we generated a skeletal muscle-specific HIF1α knockout (KO) mouse model and performed extensive metabolic phenotyping and transcriptomic profiling under both basal conditions and following acute exercise during early rest (ZT3) and active (ZT15) phases. Our findings reveal that HIF1α drives a more robust transcriptional and glycolytic response to exercise at ZT3, promoting glucose oxidation and mannose-6-phosphate production while potentially sparing fatty acid oxidation. In the absence of HIF1α, skeletal muscle metabolism shifts toward oxidative pathways at ZT3, with notable alterations in glucose fate. These results establish HIF1α as an important regulator of time-of-day-specific metabolic adaptations, integrating circadian and energetic signals to optimize substrate utilization. This work highlights the broader significance of HIF1α in coordinating circadian influences on metabolic health and exercise performance.
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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 Socratic graph.