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Bibliographic Details
Main Authors: Cheehoon Ahn, Adeline Divoux, Mingqi Zhou, Marcus M. Seldin, Lauren M. Sparks, Katie L. Whytock
Format: Artículo Open Access
Published: Wiley 2025
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Online Access:https://onlinelibrary.wiley.com/doi/10.1002/oby.24264
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Table of Contents:
  • Optimized RNA sequencing deconvolution illustrates the impact of obesity and weight loss on cell composition of human adipose tissue Cheehoon Ahn Adeline Divoux Mingqi Zhou Marcus M. Seldin Lauren M. Sparks Katie L. Whytock Obesity AbstractObjectiveCellular heterogeneity of human adipose tissue is linked to the pathophysiology of obesity and may impact the response to energy restriction and changes in fat mass. Herein, we provide an optimized pipeline to estimate cellular composition in human abdominal subcutaneous adipose tissue (ASAT) bulk RNA sequencing (RNA‐seq) datasets using a single‐nuclei RNA‐seq signature matrix.MethodsA deconvolution pipeline for ASAT was optimized by benchmarking publicly available algorithms using a signature matrix derived from ASAT single‐nuclei RNA‐seq data from 20 adults and then applied to estimate ASAT cell‐type proportions in publicly available obesity and weight loss studies.ResultsIndividuals with obesity had greater proportions of macrophages and lower proportions of adipocyte subpopulations and vascular cells compared with lean individuals. Two months of diet‐induced weight loss increased the estimated proportions of macrophages; however, 2 years of diet‐induced weight loss reduced the estimated proportions of macrophages, thereby suggesting a biphasic nature of cellular remodeling of ASAT during weight loss.ConclusionsOur 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. 10.1002/oby.24264 http://onlinelibrary.wiley.com/termsAndConditions#vor