Angiopoietin-2 in white adipose tissue improves metabolic homeostasis through enhanced angiogenesis
- The University of Texas Southwestern Medical Center, United States
- AdipoGen Life Sciences, Switzerland
Abstract
Despite many angiogenic factors playing crucial roles in metabolic homeostasis, effects of angiopoietin-2 (ANG-2) in adipose tissue (AT) remain unclear. Utilizing a doxycycline-inducible AT-specific ANG-2 overexpression mouse model, we assessed the effects of ANG-2 in AT expansion upon a high-fat diet (HFD) challenge. ANG-2 is significantly induced, with subcutaneous white AT (sWAT) displaying the highest ANG-2 expression. ANG-2 overexpressing mice show increased sWAT vascularization and are resistant to HFD-induced obesity. In addition, improved glucose and lipid metabolism are observed. Mechanistically, the sWAT displays a healthier expansion pattern with increased anti-inflammatory macrophage infiltration. Conversely, ANG-2 neutralization in HFD-challenged wild-type mice shows reduced vascularization in sWAT, associated with impaired glucose tolerance and lipid clearance. Blocking ANG-2 causes significant pro-inflammatory and pro-fibrotic changes, hallmarks of an unhealthy AT expansion. In contrast to other pro-angiogenic factors, such as vascular endothelial growth factor-A (VEGF-A), this is achieved without any enhanced beiging of white AT.
Article and author information
Author details
Funding
National Institutes of Health (P01-DK088761 R01-DK55758 R01-DK099110)
- Philipp E Scherer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Peter Tontonoz, University of California, Los Angeles, United States
Ethics
Animal experimentation: All animal experiments conducted in the present study were approved by the Institutional Animal Care and Research Advisory Committee at the University of Texas Southwestern Medical Center (APN# 2015-101207).
Version history
- Received: December 9, 2016
- Accepted: March 28, 2017
- Accepted Manuscript published: March 29, 2017 (version 1)
- Version of Record published: April 13, 2017 (version 2)
Copyright
© 2017, An et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Angiopoietin-2 in white adipose tissue improves metabolic homeostasis through enhanced angiogenesis
eLife 6:e24071.
https://doi.org/10.7554/eLife.24071
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