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 journalArticle

14 Citations (Scopus)

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 languageEnglish (US)
Article numbere24071
JournaleLife
Volume6
DOIs
StatePublished - Mar 29 2017

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Angiopoietin-2
White Adipose Tissue
Homeostasis
Tissue
Adipose Tissue
High Fat Diet
Nutrition
Tissue Expansion
Angiogenesis Inducing Agents
Fats
Glucose
Glucose Intolerance
Doxycycline
Macrophages
Subcutaneous Fat
Lipid Metabolism
Infiltration
Vascular Endothelial Growth Factor A
Anti-Inflammatory Agents
Obesity

ASJC Scopus subject areas

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

Cite this

Angiopoietin-2 in white adipose tissue improves metabolic homeostasis through enhanced angiogenesis. / An, Yu A.; Sun, Kai; Joffin, Nolwenn; Zhang, Fang; Deng, Yingfeng; Donzé, Olivier; Kusminski, Christine M.; Scherer, Philipp E.

In: eLife, Vol. 6, e24071, 29.03.2017.

Research output: Contribution to journalArticle

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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.",
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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.

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