Peer-reviewedCC BY-NC-NDIScience
Inverse directions of association of higher physical activity and higher insulin resistance with human skeletal muscle fiber-type gene expression.
14 affiliations
- 1Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
- 2Gilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
- 3Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
- 4South Karelia Social and Health Care District, Wellbeing Services County of South Karelia, South Karelia, Finland.
- 5Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
- 6Department of Public Health, University of Helsinki, Helsinki, Finland.
- 7Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.
- 8Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
- 9Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
- 10Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
- 11University of Helsinki, Faculty of Medicine, Research Programs Unit, Clinical and Molecular Metabolism (CAMM), Helsinki, Finland.
- 12Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- 13Minerva Foundation Institute for Medical Research, Helsinki, Finland.
- 14Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract
To investigate the interplay between physical activity and cardiometabolic traits in human skeletal muscle, we characterized gene expression and chromatin accessibility across skeletal muscle cell types in 263 Finnish individuals from the FUSION Tissue Biopsy Study. We analyzed single-nucleus RNA-seq data (168,309 nuclei), single-nucleus ATAC-seq data (242,069 nuclei), and bulk RNA-seq data. Lower insulin resistance (HOMA-IR) and higher total physical activity were both associated with higher proportions of Type 1 nuclei and lower proportions of Type 2x nuclei. Traits typically associated with better health-lower trait values of cardiometabolic traits such as HOMA-IR and higher physical activity levels-were associated with higher expression of energy metabolism genes and lower expression of signaling pathway genes across muscle fiber types, total pseudobulk, and to some extent in bulk tissue. HOMA-IR and physical activity appeared to have inverse and partially independent directions of association when adjusting for both traits in the same model.
Related
- Iron oxide nanoparticle-mediated elicitation enhances secondary metabolite production, antioxidant activity, and gene expression in Melia azedarach L
- Resistance to modulation of in vivo gene expression by genomic editing.
- Decoding the Physical Mechanisms of Protein-Small Molecule Association by Multiscale Kinetic Monte-Carlo Simulations
- Associations of Self-Reported Physical Activity with Gut Microbial Diversity and Community Structure in Young, Apparently Healthy Korean Men.
- Computational identification of candidate biomarkers and compounds associated with skeletal muscle insulin sensitivity improvement mediated by physical activity: an integrative multi-omics and computational chemistry study.
BibTeX
@article{ciotlos2026inverse,
title = {{Inverse directions of association of higher physical activity and higher insulin resistance with human skeletal muscle fiber-type gene expression.}},
author = {Dan L Ciotlos and Sarah C Hanks and Arushi Varshney and Michael R Erdos and Nandini Manickam and Heather M Stringham and Peter Orchard and Erin M Hill-Burns and Narisu Narisu and Lori L Bonnycastle and Michael D Sweeney and Jouko Saramies and Markku Laakso and Jaakko Tuomilehto and Timo A Lakka and Karen L Mohlke and Michael Boehnke and Francis S Collins and Heikki A Koistinen and Stephen C J Parker and Laura J Scott},
journal = {IScience},
year = {2026},
month = sep,
doi = {10.1016/j.isci.2026.117293},
url = {https://europepmc.org/article/MED/42835133},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Inverse directions of association of higher physical activity and higher insulin resistance with human skeletal muscle fiber-type gene expression.
AU - Dan L Ciotlos
AU - Sarah C Hanks
AU - Arushi Varshney
AU - Michael R Erdos
AU - Nandini Manickam
AU - Heather M Stringham
AU - Peter Orchard
AU - Erin M Hill-Burns
AU - Narisu Narisu
AU - Lori L Bonnycastle
AU - Michael D Sweeney
AU - Jouko Saramies
AU - Markku Laakso
AU - Jaakko Tuomilehto
AU - Timo A Lakka
AU - Karen L Mohlke
AU - Michael Boehnke
AU - Francis S Collins
AU - Heikki A Koistinen
AU - Stephen C J Parker
AU - Laura J Scott
PY - 2026
DA - 2026/09/24
JO - IScience
DO - 10.1016/j.isci.2026.117293
UR - https://europepmc.org/article/MED/42835133
AB - To investigate the interplay between physical activity and cardiometabolic traits in human skeletal muscle, we characterized gene expression and chromatin accessibility across skeletal muscle cell types in 263 Finnish individuals from the FUSION Tissue Biopsy Study. We analyzed single-nucleus RNA-seq data (168,309 nuclei), single-nucleus ATAC-seq data (242,069 nuclei), and bulk RNA-seq data. Lower insulin resistance (HOMA-IR) and higher total physical activity were both associated with higher proportions of Type 1 nuclei and lower proportions of Type 2x nuclei. Traits typically associated with better health-lower trait values of cardiometabolic traits such as HOMA-IR and higher physical activity levels-were associated with higher expression of energy metabolism genes and lower expression of signaling pathway genes across muscle fiber types, total pseudobulk, and to some extent in bulk tissue. HOMA-IR and physical activity appeared to have inverse and partially independent directions of association when adjusting for both traits in the same model.
SN - 2589-0042
ER -