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Unveiling adipose populations linked to metabolic health in obesity.
Cell Metab. 37, 640-655.e4 (2024)
Precision medicine is still not considered as a standard of care in obesity treatment, despite a large heterogeneity in the metabolic phenotype of individuals with obesity. One of the strongest factors influencing the variability in metabolic disease risk is adipose tissue (AT) dysfunction; however, there is little understanding of the link between distinct cell populations, cell-type-specific transcriptional programs, and disease severity. Here, we generated a comprehensive cellular map of subcutaneous and visceral AT of individuals with metabolically healthy and unhealthy obesity. By combining single-nucleus RNA-sequencing data with bulk transcriptomics and clinical parameters, we identified that mesothelial cells, adipocytes, and adipocyte-progenitor cells exhibit the strongest correlation with metabolic disease. Furthermore, we uncovered cell-specific transcriptional programs, such as the transitioning of mesothelial cells to a mesenchymal phenotype, that are involved in uncoupling obesity from metabolic disease. Together, these findings provide valuable insights by revealing biological drivers of clinical endpoints.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Adipocytes ; Adipose Tissue ; Insulin Resistance ; Insulin Sensitivity ; Mesothelial Cells ; Metabolically Healthy Obesity ; Obesity ; Precision Medicine ; Snrna-seq ; Visceral Adipose Tissue; Insulin Sensitivity; Mesothelial Cells; Subcutaneous Fat; Weight-loss; Tissue; Expression; Rna
Language
english
Publication Year
2024
HGF-reported in Year
2024
ISSN (print) / ISBN
1550-4131
e-ISSN
1932-7420
Journal
Cell Metabolism
Quellenangaben
Volume: 37,
Issue: 3,
Pages: 640-655.e4
Publisher
Elsevier
Publishing Place
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status
Peer reviewed
Institute(s)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF-Topic(s)
30201 - Metabolic Health
Research field(s)
Helmholtz Diabetes Center
PSP Element(s)
G-506501-001
Grants
Austrian Science Fund FWF
Austrian Science Fund FWF
WOS ID
001440737100001
Scopus ID
85214324306
PubMed ID
39694039
Erfassungsdatum
2024-12-20