Evidence map›Paper›PMID 40412648›Full record

ArticleMolecular metabolism2025

IL-6 decodes sex and diet-dependent circadian and metabolic rhythms.

Antía González-Vila, Ali Mohammad Ibrahim-Alasoufi, María Luengo-Mateos, Víctor Pardo-García, Alejandro Diaz-López, Belén Fernández-Rodríguez, Matti Poutanen, Claes Ohlsson, Manuel Tena-Sempere, Carlos Diéguez-González and 2 more

Erratum issuedAbstract read
In one paragraph

Article in Molecular metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Antía González-VilaPhysiology Department, Molecular Medicine and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Ali Mohammad Ibrahim-AlasoufiPhysiology Department, Molecular Medicine and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, Santiago de Compostela, Spain; Biology Department, Al-Hussein Bin Talal University, Ma'an, Jordan.
María Luengo-MateosPhysiology Department, Molecular Medicine and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Víctor Pardo-GarcíaPhysiology Department, Molecular Medicine and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Alejandro Diaz-LópezPhysiology Department, Molecular Medicine and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Belén Fernández-RodríguezPhysiology Department, Molecular Medicine and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Matti PoutanenResearch Center for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland; Turku Center for Disease Modeling, Turku, Finland.
Claes OhlssonSahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Manuel Tena-SempereDepartment of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
Carlos Diéguez-GonzálezPhysiology Department, Molecular Medicine and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
María Del Carmen García-GarcíaPhysiology Department, Molecular Medicine and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Olga Barca-MayoPhysiology Department, Molecular Medicine and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: olga.barca.mayo@usc.es.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveInterleukin-6 (IL-6) is a pleiotropic cytokine involved in immune regulation and energy metabolism. Its diurnal secretion influences core circadian components, emphasizing its critical role in circadian biology. Despite known sex differences in immune, circadian, and metabolic processes, how IL-6 integrates these processes remains poorly understood.

methodsIL6 knockout (KO) and control mice of both sexes were phenotyped for circadian and metabolic traits under standard (STD) and high-fat diet (HFD), fasting, and time-restricted feeding. Molecular analyses in muscle, liver, and hypothalamus assessed clock gene expression and IL-6 signaling pathway. Circulating sex steroid hormones were quantified to examine their contribution to the observed sex-specific phenotypes.

resultsIL-6 deficiency disrupts circadian locomotor and metabolic rhythms in a sex- and diet-dependent manner. Males exhibit impaired light-driven circadian rhythms under STD conditions and metabolic misalignment under HFD, whereas females display greater circadian resilience under STD conditions but increased vulnerability to circadian disruption during HFD. Additionally, IL-6 emerges as a novel regulator of the food-entrainable oscillator (FEO), linking food anticipatory activity and metabolic cycles under both STD and HFD in a sex-dependent manner.

conclusionsThese findings identify IL-6 as a critical mediator of circadian-metabolic plasticity, shaping sex- and diet-specific trade-offs between circadian stability and metabolic homeostasis. Our study highlights IL-6 as a potential therapeutic target for mitigating circadian misalignment-associated metabolic disorders, with implications for the timed modulation of IL-6 signaling.

Indexed as

Circadian RhythmInterleukin-6AnimalsDiet, High-FatEnergy MetabolismFemaleLiverMaleMiceMice, Inbred C57BLMice, KnockoutSex CharacteristicsSex FactorsSignal TransductionInterleukin-6interleukin-6, mouseCircadian rhythmsEnergy balanceInterleukin-6Metabolic cyclesSexual dimorphism

Identifiers

PMID40412648
PMCPMC12159943

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.