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 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.
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Yu A
authors.identifier: 0000-0002-9678-3382
authors.initials: YA
authors.lastname: An
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, United States.|Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, United States.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Joffin
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, United States.|Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Yingfeng
authors.identifier: 0000-0003-1314-5105
authors.initials: Y
authors.lastname: Deng
authors.affiliation: AdipoGen Life Sciences, Epalinges, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Donzé
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Kusminski
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, United States.|Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Philipp E
authors.identifier: 0000-0003-0680-3392
authors.initials: PE
authors.lastname: Scherer
mesh_terms: D052436:Adipose Tissue, White / Q000502:physiology*; D042702:Angiopoietin-2 / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D005947:Glucose / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D018919:Neovascularization, Physiologic
chemical_list: D042702:Angiopoietin-2; D005947:Glucose
keywords: Angiopoietin-2; adipose tissue expansion; angiogenesis; cell biology; human biology; medicine; metabolic homeostasis; mouse; obesity