Optimized RNA sequencing deconvolution illustrates the impact of obesity and weight loss on cell composition of human adipose tissue
Authors' conclusion
Our optimized high-throughput pipeline facilitates the assessment of composition changes of highly characterized cell types in large numbers of ASAT samples using low-cost bulk RNA-seq. Our data reveal novel changes in cellular heterogeneity and its association with cardiometabolic health in humans with obesity and following weight loss.
Study context
- Population
- Human abdominal subcutaneous adipose tissue (ASAT) bulk RNA sequencing (RNA-seq) datasets from publicly available obesity and weight loss studies; signature matrix from ASAT single-nuclei RNA-seq of 20 adultssignature matrix from 20 adults
- Comparison
- Obesity vs lean; before vs after diet-induced weight loss
- Outcome
- Estimated ASAT cell-type proportions
Methodological detailsbenchmarking of publicly available deconvolution algorithms, single-nuclei RNA-seq signature matrix, analysis of publicly available datasets
- Benchmarking of publicly available deconvolution algorithms
- Single-nuclei RNA-seq signature matrix
- Analysis of publicly available datasets
Main finding
As reported in the abstract
Estimated ASAT cell-type proportions, obesity vs lean
- Greater proportions of macrophages with obesity vs lean
- Lower proportions of adipocyte subpopulations and vascular cells with obesity vs lean
Further findings
- 2 months of diet-induced weight loss increased estimated macrophage proportions
- 2 years of diet-induced weight loss reduced estimated macrophage proportions
- Suggests a biphasic nature of cellular remodeling of ASAT during weight loss
Original publication
Optimized RNA sequencing deconvolution illustrates the impact of obesity and weight loss on cell composition of human adipose tissue. Obesity (Silver Spring). Published 2 April 2025. doi:10. 1002/ oby. 24264
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