Multi-omics integration reveals the role of PFOS in sarcopenia via ESRRG and RBP4: from computational prediction to experimental validation
- 1Department of Orthopaedics, Chengdu Fifth People’s Hospital
- 2Department of Radiology, Medical Imaging Center, West China Second University Hospital, Sichuan University
Abstract
Background: Perfluorooctane sulfonate (PFOS) has been shown to cause multi-organ dysfunction; however, the specific mechanisms underlying its association with sarcopenia remain unclear.
Methods: Network toxicology analysis was performed to identify potential molecular targets and related signaling pathways involved in PFOS-induced sarcopenia. Molecular docking and dynamics simulations further screened stable PFOS–target interactions. Single-nucleus RNA-seq analysis was used to assess cell-type-specific PFOS-related signatures and ESRRG/RBP4-associated regulatory pathways in skeletal muscle. Finally, in vitro experiments were performed to evaluate the effects of PFOS on myogenic differentiation.
Results: Network toxicology identified seven potential targets enriched in the PPAR signaling pathway. Molecular simulations indicated stable binding interactions between PFOS and ESRRG/RBP4. Single-nucleus RNA-seq analysis suggested that mast cells may represent a potential PFOS-responsive cell population and revealed cytoskeleton-related pathway alterations associated with ESRRG and RBP4. In vitro experiments further demonstrated that PFOS markedly inhibited myogenic differentiation, accompanied by downregulation of related protein expression.
Conclusion: Our study demonstrates that exposure to PFOS is associated with an increased risk of sarcopenia and identifies ESRRG and RBP4 as key mediators of PFOS-associated myotoxicity.
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BibTeX
@article{yang2026multiomics,
title = {{Multi-omics integration reveals the role of PFOS in sarcopenia via ESRRG and RBP4: from computational prediction to experimental validation}},
author = {Xingyao Yang and Xin Wang and Shuxing Xing and Zhangzhen Du},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1926144},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1926144/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multi-omics integration reveals the role of PFOS in sarcopenia via ESRRG and RBP4: from computational prediction to experimental validation
AU - Xingyao Yang
AU - Xin Wang
AU - Shuxing Xing
AU - Zhangzhen Du
PY - 2026
DA - 2026/10/08
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1926144
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1926144/full
AB - Background: Perfluorooctane sulfonate (PFOS) has been shown to cause multi-organ dysfunction; however, the specific mechanisms underlying its association with sarcopenia remain unclear. Methods: Network toxicology analysis was performed to identify potential molecular targets and related signaling pathways involved in PFOS-induced sarcopenia. Molecular docking and dynamics simulations further screened stable PFOS–target interactions. Single-nucleus RNA-seq analysis was used to assess cell-type-specific PFOS-related signatures and ESRRG/RBP4-associated regulatory pathways in skeletal muscle. Finally, in vitro experiments were performed to evaluate the effects of PFOS on myogenic differentiation. Results: Network toxicology identified seven potential targets enriched in the PPAR signaling pathway. Molecular simulations indicated stable binding interactions between PFOS and ESRRG/RBP4. Single-nucleus RNA-seq analysis suggested that mast cells may represent a potential PFOS-responsive cell population and revealed cytoskeleton-related pathway alterations associated with ESRRG and RBP4. In vitro experiments further demonstrated that PFOS markedly inhibited myogenic differentiation, accompanied by downregulation of related protein expression. Conclusion: Our study demonstrates that exposure to PFOS is associated with an increased risk of sarcopenia and identifies ESRRG and RBP4 as key mediators of PFOS-associated myotoxicity.
SN - 1663-9812
ER -