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Peer-reviewedCC BYGenes

Human Subcutaneous Adipose Transcriptomes Link Mitochondrial Transcription to Metabolic Heterogeneity in Obesity.

  • Shuang Bai1
  • Meng Qi2,3
  • Shuang Wu1
  • Junzhu Wang1
  • Qing Yang3
  • Yajuan Cui4
  • Siyuan Ma1
  • Dongling Wang5
5 affiliations
  1. 1School of Kinesiology and Health, Capital University of Physical Education and Sports, Beijing 100191, China.
  2. 2Division of Sports Science and Physical Education, Tsinghua University, Beijing 100084, China.
  3. 3College of Forestry, Beijing Forestry University, Beijing 100083, China.
  4. 4Beijing Institute of Nutritional Resources Company Limited, Beijing 100069, China.
  5. 5Central Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China.
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Abstract

Background

Metabolically healthy obesity and metabolically unhealthy obesity may occupy different positions along a continuum of adipose-tissue dysfunction, but stable molecular distinctions remain uncertain.Methods

We integrated three public human subcutaneous-adipose-tissue transcriptomic datasets while preserving participant and platform independence. GSE244118 was used for discovery, GSE152991 was restricted to 14 participants not overlapping with the discovery cohort, and GSE55200 provided cross-platform supportive evidence. We performed differential-expression analysis, correlation-adjusted Reactome testing, direction-aware cross-dataset integration, discovery-defined module scoring, and adipose-tissue deconvolution.Results

Fifty genes met conventional thresholds for metabolically unhealthy versus metabolically healthy obesity in the discovery dataset, but none passed the prespecified fold-change-aware test or strict cross-dataset replication. Among 1570 shared Reactome pathways, 409 reached false-discovery rate < 0.05 in signed-Z integration and 387 had concordant directions across all datasets. Metabolically unhealthy obesity consistently showed lower mitochondrial translation, respiratory-chain, and energy-metabolism programs, accompanied by secondary increases in extracellular-matrix remodeling. A discovery-defined mitochondrial module was lower in metabolically unhealthy obesity in synthesis restricted to non-discovery datasets under both rank and z-mean scoring. The 14-person holdout alone did not establish a significant module difference, and the extracellular-matrix module synthesis was nonsignificant. Ordered cross-sectional patterns and composition sensitivity described tissue-level associations.Conclusions

Metabolic obesity heterogeneity was therefore more reproducible at pathway and module levels than at the single-gene level. Unresolved clinical confounding and bulk tissue composition limit functional and causal interpretation.

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Cite

BibTeXRIS
BibTeX
@article{bai2026human,
  title = {{Human Subcutaneous Adipose Transcriptomes Link Mitochondrial Transcription to Metabolic Heterogeneity in Obesity.}},
  author = {Shuang Bai and Meng Qi and Shuang Wu and Junzhu Wang and Qing Yang and Yajuan Cui and Siyuan Ma and Dongling Wang},
  journal = {Genes},
  year = {2026},
  month = sep,
  doi = {10.3390/genes17101199},
  url = {https://europepmc.org/article/MED/42938315},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Human Subcutaneous Adipose Transcriptomes Link Mitochondrial Transcription to Metabolic Heterogeneity in Obesity.
AU  - Shuang Bai
AU  - Meng Qi
AU  - Shuang Wu
AU  - Junzhu Wang
AU  - Qing Yang
AU  - Yajuan Cui
AU  - Siyuan Ma
AU  - Dongling Wang
PY  - 2026
DA  - 2026/09/28
JO  - Genes
DO  - 10.3390/genes17101199
UR  - https://europepmc.org/article/MED/42938315
AB  - Background  Metabolically healthy obesity and metabolically unhealthy obesity may occupy different positions along a continuum of adipose-tissue dysfunction, but stable molecular distinctions remain uncertain.Methods  We integrated three public human subcutaneous-adipose-tissue transcriptomic datasets while preserving participant and platform independence. GSE244118 was used for discovery, GSE152991 was restricted to 14 participants not overlapping with the discovery cohort, and GSE55200 provided cross-platform supportive evidence. We performed differential-expression analysis, correlation-adjusted Reactome testing, direction-aware cross-dataset integration, discovery-defined module scoring, and adipose-tissue deconvolution.Results  Fifty genes met conventional thresholds for metabolically unhealthy versus metabolically healthy obesity in the discovery dataset, but none passed the prespecified fold-change-aware test or strict cross-dataset replication. Among 1570 shared Reactome pathways, 409 reached false-discovery rate < 0.05 in signed-Z integration and 387 had concordant directions across all datasets. Metabolically unhealthy obesity consistently showed lower mitochondrial translation, respiratory-chain, and energy-metabolism programs, accompanied by secondary increases in extracellular-matrix remodeling. A discovery-defined mitochondrial module was lower in metabolically unhealthy obesity in synthesis restricted to non-discovery datasets under both rank and z-mean scoring. The 14-person holdout alone did not establish a significant module difference, and the extracellular-matrix module synthesis was nonsignificant. Ordered cross-sectional patterns and composition sensitivity described tissue-level associations.Conclusions  Metabolic obesity heterogeneity was therefore more reproducible at pathway and module levels than at the single-gene level. Unresolved clinical confounding and bulk tissue composition limit functional and causal interpretation.
SN  - 2073-4425
ER  -