Evidence map›Paper›PMID 42537502›Full record

ArticleEBioMedicine2026

Skeletal muscle reprogramming of metabolic, ribosomal and developmental pathways contributes to Roux-en-Y gastric bypass-induced adaptation in women.

Chantal A Pileggi, Dhanuddara Mohottalage, Luke S Kennedy, Majid Nikpay, Lauren M K Hamilton, Martín Roffe, Michel N Kanaan, Amer Jarrar, Nicole Kolozsvari, Dongdong Wang and 6 more

Abstract read
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In one paragraph

Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Chantal A PileggiDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
Dhanuddara MohottalageDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
Luke S KennedyDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
Majid NikpayDivision of Cardiology, Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Lauren M K HamiltonDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
Martín RoffeDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Michel N KanaanDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
Amer JarrarDepartment of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.
Nicole KolozsvariDepartment of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.
Dongdong WangDepartment of Medicine, Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Ontario, Canada.
Miroslava Cuperlovic-CulfNational Research Council of Canada, Digital Technologies Research Centre, Ottawa, Canada.
Tommy AlainDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Gregory R SteinbergDepartment of Medicine, Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Ontario, Canada.
Ruth McPhersonDivision of Cardiology, Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Robert DentDivision of Endocrinology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Mary-Ellen HarperDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: mharper@uottawa.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUnderstanding how skeletal muscle responds to weight loss is crucial for developing targeted strategies to manage obesity and promote sustained improvement in metabolic health. Here, we investigated the molecular mechanisms underlying skeletal muscle reprogramming of gene expression and metabolic activity following Roux-en-Y gastric bypass (RYGB).

methodsForty-one women were studied before and one year after RYGB surgery. We leveraged multi-omics (DNA methylomics and transcriptomics) and machine learning approaches to complement muscle metabolic analyses and clinical data to identify mechanisms underlying RYGB-induced muscle metabolic reprogramming.

findingsRYGB markedly decreased body weight and fat mass and improved metabolic health. Integrative analysis of vastus lateralis muscle identified 8233 genes with differentially methylated regions and 2173 differentially expressed genes post-RYGB surgery, of which 1197 genes were both differentially methylated and differentially expressed. Promoter hypomethylation was associated with the enhanced expression of transcription factors involved in skeletal muscle development and ribosomal subunits. In contrast, expression of genes encoding mitochondrial proteins decreased despite increases in mitochondrial content and enhanced mitochondrial function in skeletal muscle post-RYGB. Pre-operative muscle OXPHOS capacity, and expression of skeletal muscle hypertrophy and differentiation genes MYOC and EHMT2 were associated with weight loss success.

interpretationRYGB improves systemic metabolic health and induces sustained skeletal muscle bioenergetic reprogramming characterised by enhanced expression of genes involved in myogenesis and protein translation, but decreased expression of genes involved in mitochondrial metabolism, which may reflect improved mitochondrial quality and function. These findings advance our understanding of skeletal muscle metabolic responses to weight loss and of individual variability in metabolic phenotypes.

fundingCanadian Institutes of Health Research (CIHR PJT183651-M-EH, 201709FDN-CEBA-116200-GRS), Diabetes Canada Investigator Award grant OG-3-22-5645-GS (GRS), J. Bruce Duncan Endowed Chair in Metabolic Diseases (GRS), Tier 1 Canada Research Chair in Mitochondrial Bioenergetics and Metabolic Health (M-EH), Tier 1 Canada Research Chair in Metabolic Diseases (GRS).

Indexed as

Adaptation, PhysiologicalGastric BypassMuscle, SkeletalRibosomesAdultDNA MethylationFemaleGene Expression ProfilingGene Expression RegulationHumansMetabolic ReprogrammingMiddle AgedMultiomicsMuscle DevelopmentObesityBariatric surgeryDNA methylationEpigeneticsMetabolismMitochondriaObesityRibosomeTranscriptomicsType 2 diabetesWeight loss

Identifiers

PMID42537502
PMCPMC13452326

What OpenQuestion 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 OpenQuestion graph.