2. Academic Validation
  3. Gpc3 selectively suppresses subcutaneous adipogenesis in diet-induced obesity

Gpc3 selectively suppresses subcutaneous adipogenesis in diet-induced obesity

  • PLoS Biol. 2026 Mar 4;24(3):e3003700. doi: 10.1371/journal.pbio.3003700.
Yan Li 1 2,  Ming Tao 3,  Carlos F Ibáñez 1 4 5 6 7,  Meng Xie 5 6 8 9
Affiliations

Affiliations

  • 1 Chinese Institute for Brain Research, Zhongguancun Life Science Park, Beijing, China.
  • 2 Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
  • 3 Department of General Surgery, Peking University Third Hospital, Beijing, China.
  • 4 School of Life Sciences, Peking University, Beijing, China.
  • 5 Peking-Tsinghua Center for Life Sciences, Beijing, China.
  • 6 PKU-IDG/McGovern Institute for Brain Research, Beijing, China.
  • 7 Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
  • 8 School of Psychological and Cognitive Sciences, Peking University, Beijing Key Laboratory of Behavior and Mental Health, Beijing, China.
  • 9 Biosciences and Nutrition Unit, Department of Medicine Huddinge, Karolinska Institute, Huddinge, Sweden.
PMID: 41779769 DOI: 10.1371/journal.pbio.3003700
Abstract

Subcutaneous and visceral adipose depots employ distinct expansion strategies in response to dietary cues, yet the molecular regulators underlying these depot-specific adaptations remain poorly understood. Through integrated proteomic profiling of human subcutaneous and visceral adipose tissues from paired obese/non-obese donors and temporal transcriptomic analysis of mouse adipose stem and progenitor cells (ASPCs) during dietary transitions, we identified Glypican 3 (Gpc3) as an obesity-responsive gene exhibiting reciprocal expression patterns between depots. ASPC-specific Gpc3 deletion in mice amplified high-fat diet-induced weight and fat mass gain, with a selective enhancement of expansion in inguinal white adipose tissue (WAT) without affecting epididymal WAT. Mechanistically, Gpc3 loss biased ASPC fate toward adipogenesis over proliferation through depot-specific modulation of canonical Wnt signaling. These findings establish Gpc3 as a regulator for regional adipose plasticity, offering a molecular target for reprogramming pathological fat distribution in obesity and related metabolic disorders.

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