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<p>Human white adipose tissue undergoes major remodelling during sustained weight gain that may compromise tissue function and drive cardiometabolic comorbidities. Although weight loss reverses many of these complications, the cellular and molecular adaptations of adipose tissue to different weight loss interventions are poorly understood. Here we show how abdominal subcutaneous adipose tissue (SAT) in men and women with severe obesity adapts to modest lifestyle-induced (8–10%) weight loss followed by substantial bariatric surgery-induced (20–45%) weight loss, using single-nucleus RNA sequencing (snRNA-seq) combined with bulk RNA-seq, and three-dimensional light-sheet fluorescence microscopy. To enable interactive exploration, all snRNA-seq data are available in a browsable format on the Single Cell Portal (<a href="http://singlecell.broadinstitute.org/single_cell?type=study&amp;page=1&amp;terms=SCP2849">SCP2849</a>). Lifestyle-induced weight loss activated proadipogenic gene programmes in progenitor cells, indicating early beneficial effects on SAT. Subsequent surgery-induced weight loss drove profound compositional and transcriptional remodelling of SAT, including increased vascularization and marked reduction of myeloid cell populations. Collectively, our study indicates that following major and sustained weight loss, SAT from individuals with severe obesity has the capacity to return to a state comparable to that observed in lean individuals.</p>

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Single-cell-resolved transcriptional dynamics of human subcutaneous adipose tissue during lifestyle- and bariatric surgery-induced weight loss

  • 期刊论文

  • 发表日期：

    2026年1月12日

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  • Anne Loft,
  • Rasmus Rydbirk,
  • Ellen Gammelmark Klinggaard,
  • Elvira Laila Van Hauwaert,
  • Charlotte Wilhelmina Wernberg,
  • Andreas Fønss Møller,
  • Trine Vestergaard Dam,
  • Mohamed Nabil Hassan,
  • Babukrishna Maniyadath,
  • Ronni Nielsen,
  • Aleksander Krag,
  • Joanna Kalucka,
  • Søren Fisker Schmidt,
  • Mette Enok Munk Lauridsen,
  • Jesper Grud Skat Madsen,
  • Susanne Mandrup

摘要

Human white adipose tissue undergoes major remodelling during sustained weight gain that may compromise tissue function and drive cardiometabolic comorbidities. Although weight loss reverses many of these complications, the cellular and molecular adaptations of adipose tissue to different weight loss interventions are poorly understood. Here we show how abdominal subcutaneous adipose tissue (SAT) in men and women with severe obesity adapts to modest lifestyle-induced (8–10%) weight loss followed by substantial bariatric surgery-induced (20–45%) weight loss, using single-nucleus RNA sequencing (snRNA-seq) combined with bulk RNA-seq, and three-dimensional light-sheet fluorescence microscopy. To enable interactive exploration, all snRNA-seq data are available in a browsable format on the Single Cell Portal (SCP2849). Lifestyle-induced weight loss activated proadipogenic gene programmes in progenitor cells, indicating early beneficial effects on SAT. Subsequent surgery-induced weight loss drove profound compositional and transcriptional remodelling of SAT, including increased vascularization and marked reduction of myeloid cell populations. Collectively, our study indicates that following major and sustained weight loss, SAT from individuals with severe obesity has the capacity to return to a state comparable to that observed in lean individuals.