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

被引：69

作者：

An, Yu A. ^{[1
]}

Sun, Kai ^{[1
,2
]}

Joffin, Nolwenn ^{[1
]}

Zhang, Fang ^{[1
,3
]}

Deng, Yingfeng ^{[1
]}

Donze, Olivier ^{[4
]}

Kusminski, Christine M. ^{[1
]}

Scherer, Philipp E. ^{[1
,5
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Touchstone Diabet Ctr, Dallas, TX 75390 USA

[2] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Ctr Metab & Degenerat Dis, Houston, TX 77030 USA

[3] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China

[4] AdipoGen Life Sci, Epalinges, Switzerland

[5] Univ Texas Southwestern Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA

来源：

ELIFE | 2017年 / 6卷

基金：

美国国家卫生研究院;

关键词：

DIET-INDUCED OBESITY; VEGF-A; STIMULATES ANGIOGENESIS; INSULIN SENSITIVITY; MICE; INFLAMMATION; VASCULATURE; DYSFUNCTION; MODULATION; EXPRESSION;

D O I：

10.7554/eLife.24071

中图分类号：

Q [生物科学];

学科分类号：

090105 [作物生产系统与生态工程];

摘要：

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 proinflammatory 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.

引用

页数：22

共 41 条

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