Thomas Franz Erich Willnow

SORLA is required for insulin-induced expansion of the adipocyte precursor pool in visceral fat

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DOI

  • Vanessa Schmidt, Max Delbrueck Center for Molecular Medicine
  • ,
  • Carla Horváth, ETH Zürich
  • ,
  • Hua Dong, ETH Zürich
  • ,
  • Matthias Blüher, Leipzig University
  • ,
  • Per Qvist
  • ,
  • Christian Wolfrum, ETH Zürich
  • ,
  • Thomas E Willnow

Visceral adipose tissue shows remarkable plasticity, constantly replacing mature adipocytes from an inherent pool of adipocyte precursors. The number of precursors is set in the juvenile organism and remains constant in adult life. Which signals drive precursor pool expansion in juveniles and why they operate in visceral but not in subcutaneous white adipose tissue (WAT) are unclear. Using mouse models, we identified the insulin-sensitizing receptor SORLA as a molecular factor explaining the distinct proliferative capacity of visceral WAT. High levels of SORLA activity in precursors of juvenile visceral WAT prime these cells for nutritional stimuli provided through insulin, promoting mitotic expansion of the visceral precursor cell pool in overfed juvenile mice. SORLA activity is low in subcutaneous precursors, blunting their response to insulin and preventing diet-induced proliferation of this cell type. Our findings provide a molecular explanation for the unique proliferative properties of juvenile visceral WAT, and for the genetic association of SORLA with visceral obesity in humans.

Original languageEnglish
Article numbere202006058
JournalThe Journal of Cell Biology
Volume220
Issue12
Number of pages21
ISSN0021-9525
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

© 2021 Schmidt et al.

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