Evidence mapPaperPMID 40627397Full record

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.

Amy M Ehrlich, Kirstin A MacGregor, Stephen P Ashcroft, Lewin Small, Ali Altıntaş, Alexander V Chibalin, Matthias Anagho-Mattanovich, Ben Stocks, Thomas Moritz, Jonas T Treebak and 1 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. 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 · 2025
    Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Amy M EhrlichNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.ORCID 0000-0003-4830-1024
Kirstin A MacGregorIntegrative Physiology Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm SE-171 77, Sweden.
Stephen P AshcroftNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.
Lewin SmallNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.
Ali AltıntaşNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.
Alexander V ChibalinIntegrative Physiology Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm SE-171 77, Sweden.ORCID 0000-0002-6339-6271
Matthias Anagho-MattanovichNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.
Ben StocksNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.
Thomas MoritzNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.
Jonas T TreebakNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.ORCID 0000-0003-1488-7012
Juleen R ZierathNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.ORCID 0000-0001-6891-7497

Funding

EC | ERC | HORIZON EUROPE European Research Council (ERC) AdG 1011420930Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation) 2023.0312Novo Nordisk Fonden (NNF) NNF14OC0011493Novo Nordisk Fonden (NNF) NNF17OC0030088Novo Nordisk Fonden (NNF) NNF18CC0034900Novo Nordisk Fonden (NNF) NNF23SA0084103Svenska Diabetesstiftelsen (Swedish Diabetes Foundation) DIA2021-645Swedish Research Council for Sport Science P2017-0103Swedish Research Council for Sport Science P2018-0097Vetenskapsrådet (VR) 2015-00165
6 · The paper itself

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.

Indexed as

Circadian RhythmHypoxia-Inducible Factor 1, alpha SubunitMuscle, SkeletalPhysical Conditioning, AnimalAnimalsGlucoseGlycolysisMaleMiceMice, Inbred C57BLMice, KnockoutGlucoseHif1a protein, mouseHypoxia-Inducible Factor 1, alpha Subunitcircadianenergy metabolismexercisemetabolismtranscription factor

Identifiers

PMID40627397
PMCPMC12280960

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.