Angiopoietin-2 in white adipose tissue improves metabolic homeostasis through enhanced angiogenesis

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.

DOI: http://dx.doi.org/10.7554/eLife.24071.001

Contributors

Peter Tontonoz: Role: Reviewing editor

Journal

Journal ID (nlm-ta): eLife

Journal ID (iso-abbrev): Elife

Journal ID (hwp): eLife

Journal ID (publisher-id): eLife

Title: eLife

Publisher: eLife Sciences Publications, Ltd

ISSN (Electronic): 2050-084X

Publication date (Electronic): 29 March 2017

Publication date Collection: 2017

Volume: 6

Affiliations

[1 ]deptTouchstone Diabetes Center, Department of Internal Medicine , The University of Texas Southwestern Medical Center , Dallas, United States

[2 ]deptCenter for Metabolic and Degenerative Diseases , The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston , Houston, United States

[3 ]Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China

[4 ]AdipoGen Life Sciences , Epalinges, Switzerland

[5 ]deptDepartment of Cell Biology , The University of Texas Southwestern Medical Center , Dallas, United States

University of California, Los Angeles , United States

University of California, Los Angeles , United States

Author notes

philipp.scherer@ 123456utsouthwestern.edu

[†]

These authors contributed equally to this work.

Article

Publisher ID: 24071

DOI: 10.7554/eLife.24071

PMC ID: 5391203

PubMed ID: 28355132

Copyright statement: © 2017, An et al

License:

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Product

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: P01-DK088761

Award Recipient : Philipp E Scherer

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: R01-DK55758

Award Recipient : Philipp E Scherer

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: R01-DK099110

Award Recipient : Philipp E Scherer

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Categories

Subject: Research Article

Subject: Cell Biology

Subject: Human Biology and Medicine

Custom metadata

elife-xml-version 2.5

Author impact statement Gain- and loss-of-function studies highlight the important role for angiopoietin-2 to maintain adipose tissue health during metabolic challenges.