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.
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6 December 2021
Article|
November 15 2021
SORLA is required for insulin-induced expansion of the adipocyte precursor pool in visceral fat
Vanessa Schmidt
,
1
Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany
Correspondence to Vanessa Schmidt: vanessa.schmidt-krueger@mdc-berlin.de
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Carla Horváth,
Carla Horváth
2
Laboratory of Translational Nutrition Biology, ETH Zurich, Schwerzenbach, Switzerland
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Hua Dong,
Hua Dong
2
Laboratory of Translational Nutrition Biology, ETH Zurich, Schwerzenbach, Switzerland
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Matthias Blüher,
Matthias Blüher
3
Department of Medicine, University of Leipzig, Leipzig, Germany
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Per Qvist
,
Per Qvist
4
Department of Biomedicine, Aarhus University, Aarhus, Denmark
5
Centre for Genomics and Personalized Medicine, Aarhus University, Aarhus, Denmark
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Christian Wolfrum,
Christian Wolfrum
2
Laboratory of Translational Nutrition Biology, ETH Zurich, Schwerzenbach, Switzerland
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Thomas E. Willnow
1
Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany
4
Department of Biomedicine, Aarhus University, Aarhus, Denmark
Thomas E. Willnow: willnow@mdc-berlin.de
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Carla Horváth
2
Laboratory of Translational Nutrition Biology, ETH Zurich, Schwerzenbach, Switzerland
Hua Dong
2
Laboratory of Translational Nutrition Biology, ETH Zurich, Schwerzenbach, Switzerland
Matthias Blüher
3
Department of Medicine, University of Leipzig, Leipzig, Germany
Per Qvist
4
Department of Biomedicine, Aarhus University, Aarhus, Denmark
5
Centre for Genomics and Personalized Medicine, Aarhus University, Aarhus, Denmark
Christian Wolfrum
2
Laboratory of Translational Nutrition Biology, ETH Zurich, Schwerzenbach, Switzerland
Correspondence to Vanessa Schmidt: vanessa.schmidt-krueger@mdc-berlin.de
Thomas E. Willnow: willnow@mdc-berlin.de
Received:
June 10 2020
Revision Received:
June 19 2021
Accepted:
September 08 2021
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding
Funder(s):
European Research Council
- Award Id(s): 335692
Funder(s):
Helmholtz Association
- Award Id(s): iCEMED HA-314,AMPro ZT-0026
Funder(s):
Novo Nordisk Fonden
© 2021 Schmidt et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (12): e202006058.
Article history
Received:
June 10 2020
Revision Received:
June 19 2021
Accepted:
September 08 2021
Citation
Vanessa Schmidt, Carla Horváth, Hua Dong, Matthias Blüher, Per Qvist, Christian Wolfrum, Thomas E. Willnow; SORLA is required for insulin-induced expansion of the adipocyte precursor pool in visceral fat. J Cell Biol 6 December 2021; 220 (12): e202006058. doi: https://doi.org/10.1083/jcb.202006058
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