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

Yu A. An; Kai Sun; Nolwenn Joffin; Fang Zhang; Yingfeng Deng; Olivier Donzé; Christine M. Kusminski; Philipp E. Scherer

doi:10.7554/eLife.24071

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

Yu A. An, Kai Sun, Nolwenn Joffin, Fang Zhang, Yingfeng Deng, Olivier Donzé, Christine M. Kusminski, Philipp E. Scherer

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

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 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.

Original language	English (US)
Article number	e24071
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.24071
State	Published - Mar 29 2017

ASJC Scopus subject areas

Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)

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10.7554/eLife.24071

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@article{227f9dc9c0bb46a1b632ee80eae19c6a,

title = "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 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.",

author = "An, {Yu A.} and Kai Sun and Nolwenn Joffin and Fang Zhang and Yingfeng Deng and Olivier Donz{\'e} and Kusminski, {Christine M.} and Scherer, {Philipp E.}",

note = "Funding Information: We thank Dr. Bob Hammer and the Transgenic Core Facility at UTSW for the generation of the transgenic lines and the Metabolic Phenotyping Core, Pathology Core, and Flow Cytometry Core at UTSW for their excellent experimental assistance. We are also grateful to Dr. Vivian Paschoal in the Touchstone Diabetes Center at UTSW for her guidance and assistance in data analysis. This study was supported by US National Institutes of Health (NIH) grants P01-DK088761, R01-DK55758 and R01-DK099110 (PES). The funding agencies had no roles in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: {\textcopyright} An et al.",

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T1 - Angiopoietin-2 in white adipose tissue improves metabolic homeostasis through enhanced angiogenesis

AU - An, Yu A.

AU - Sun, Kai

AU - Joffin, Nolwenn

AU - Zhang, Fang

AU - Deng, Yingfeng

AU - Donzé, Olivier

AU - Kusminski, Christine M.

AU - Scherer, Philipp E.

N1 - Funding Information: We thank Dr. Bob Hammer and the Transgenic Core Facility at UTSW for the generation of the transgenic lines and the Metabolic Phenotyping Core, Pathology Core, and Flow Cytometry Core at UTSW for their excellent experimental assistance. We are also grateful to Dr. Vivian Paschoal in the Touchstone Diabetes Center at UTSW for her guidance and assistance in data analysis. This study was supported by US National Institutes of Health (NIH) grants P01-DK088761, R01-DK55758 and R01-DK099110 (PES). The funding agencies had no roles in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: © An et al.

PY - 2017/3/29

Y1 - 2017/3/29

N2 - 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.

AB - 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.

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

Abstract

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