Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning

J Exp Med. 2018 Feb 5;215(2):611-626. doi: 10.1084/jem.20171012. Epub 2018 Jan 5.

Abstract

Angiogenesis plays an instrumental role in the modulation of adipose tissue mass and metabolism. Targeting adipose vasculature provides an outstanding opportunity for treatment of obesity and metabolic disorders. Here, we report the physiological functions of VEGFR1 in the modulation of adipose angiogenesis, obesity, and global metabolism. Pharmacological inhibition and genetic deletion of endothelial VEGFR1 augmented adipose angiogenesis and browning of subcutaneous white adipose tissue, leading to elevated thermogenesis. In a diet-induced obesity model, endothelial-VEGFR1 deficiency demonstrated a potent anti-obesity effect by improving global metabolism. Along with metabolic changes, fatty liver and insulin sensitivity were also markedly improved in VEGFR1-deficient high fat diet (HFD)-fed mice. Together, our data indicate that targeting of VEGFR1 provides an exciting new opportunity for treatment of obesity and metabolic diseases, such as liver steatosis and type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / blood supply*
  • Adipose Tissue / metabolism*
  • Adipose Tissue, Brown / blood supply
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / blood supply
  • Adipose Tissue, White / metabolism
  • Animals
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Endothelium, Vascular / metabolism*
  • Female
  • Metabolic Diseases / metabolism
  • Metabolic Diseases / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neovascularization, Physiologic
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / therapy
  • Thermogenesis
  • Vascular Endothelial Growth Factor Receptor-1 / deficiency*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

  • Vascular Endothelial Growth Factor Receptor-1