Large-Scale Transcriptomic Meta-Analysis of Mouse Liver Responses to High-Fat Diet Identifies a Reproducible Core and Duration-Associated Variation
- 1Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Republic of Korea
- 2R&D Center, Ebiogen Inc., Seoul 04785, Republic of Korea
Abstract
High-fat diet (HFD)-fed mice are widely used to investigate hepatic responses relevant to metabolic dysfunction-associated steatotic liver disease (MASLD), but reproducibility across experiments remains unclear. We performed a multilevel meta-analysis of 64 mouse liver RNA-sequencing GEO Series (GSEs) comprising 105 HFD-versus-control contrasts and compared the results with three human liver cohorts relevant to MASLD. Among 18,234 mouse genes, 6920 showed significant pooled HFD effects, whereas only 59 met all three study-defined reproducibility criteria: pooled FDR < 0.05, a 95% prediction interval excluding zero, and ≥80% of evaluable GSEs matching the pooled-effect direction (GSE-balanced directional consistency). These 59 genes constituted a high-confidence reproducible subset. Twenty-five Hallmark pathways showed significant pooled enrichment, and HFD duration was associated with 2744 gene-level effects and multiple Hallmark pathways. Mouse–human correspondence was weak, but among 10,658 one-to-one orthologs, mouse directional consistency was associated with the odds of a same-direction human effect (OR 1.075 per 10-percentage-point increase; 95% CI 1.035–1.115; p = 1.5 × 10−4). The hepatic HFD response therefore includes a small reproducible core within a broader duration-sensitive transcriptional response, while greater cross-experiment recurrence in mice was associated with modestly higher directional concordance in MASLD-relevant human liver cohorts, without constituting direct model validation.
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BibTeX
@article{chung2026largescale,
title = {{Large-Scale Transcriptomic Meta-Analysis of Mouse Liver Responses to High-Fat Diet Identifies a Reproducible Core and Duration-Associated Variation}},
author = {Oksung Chung and Ki Moon Seong and Sung Han Shim},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219459},
url = {https://www.mdpi.com/1422-0067/27/21/9459},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Large-Scale Transcriptomic Meta-Analysis of Mouse Liver Responses to High-Fat Diet Identifies a Reproducible Core and Duration-Associated Variation
AU - Oksung Chung
AU - Ki Moon Seong
AU - Sung Han Shim
PY - 2026
DA - 2026/10/23
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219459
UR - https://www.mdpi.com/1422-0067/27/21/9459
AB - High-fat diet (HFD)-fed mice are widely used to investigate hepatic responses relevant to metabolic dysfunction-associated steatotic liver disease (MASLD), but reproducibility across experiments remains unclear. We performed a multilevel meta-analysis of 64 mouse liver RNA-sequencing GEO Series (GSEs) comprising 105 HFD-versus-control contrasts and compared the results with three human liver cohorts relevant to MASLD. Among 18,234 mouse genes, 6920 showed significant pooled HFD effects, whereas only 59 met all three study-defined reproducibility criteria: pooled FDR < 0.05, a 95% prediction interval excluding zero, and ≥80% of evaluable GSEs matching the pooled-effect direction (GSE-balanced directional consistency). These 59 genes constituted a high-confidence reproducible subset. Twenty-five Hallmark pathways showed significant pooled enrichment, and HFD duration was associated with 2744 gene-level effects and multiple Hallmark pathways. Mouse–human correspondence was weak, but among 10,658 one-to-one orthologs, mouse directional consistency was associated with the odds of a same-direction human effect (OR 1.075 per 10-percentage-point increase; 95% CI 1.035–1.115; p = 1.5 × 10−4). The hepatic HFD response therefore includes a small reproducible core within a broader duration-sensitive transcriptional response, while greater cross-experiment recurrence in mice was associated with modestly higher directional concordance in MASLD-relevant human liver cohorts, without constituting direct model validation.
SN - 1422-0067
ER -