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

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

ASJC Scopus subject areas

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

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