VEGFB/VEGFR1-Induced Expansion of Adipose Vasculature Counteracts Obesity and Related Metabolic Complications

Cell Metab. 2016 Apr 12;23(4):712-24. doi: 10.1016/j.cmet.2016.03.004.

Abstract

Impaired angiogenesis has been implicated in adipose tissue dysfunction and the development of obesity and associated metabolic disorders. Here, we report the unexpected finding that vascular endothelial growth factor B (VEGFB) gene transduction into mice inhibits obesity-associated inflammation and improves metabolic health without changes in body weight or ectopic lipid deposition. Mechanistically, the binding of VEGFB to VEGF receptor 1 (VEGFR1, also known as Flt1) activated the VEGF/VEGFR2 pathway and increased capillary density, tissue perfusion, and insulin supply, signaling, and function in adipose tissue. Furthermore, endothelial Flt1 gene deletion enhanced the effect of VEGFB, activating the thermogenic program in subcutaneous adipose tissue, which increased the basal metabolic rate, thus preventing diet-induced obesity and related metabolic complications. In obese and insulin-resistant mice, Vegfb gene transfer, together with endothelial Flt1 gene deletion, induced weight loss and mitigated the metabolic complications, demonstrating the therapeutic potential of the VEGFB/VEGFR1 pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / blood supply*
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic
  • Obesity / complications
  • Obesity / metabolism*
  • Obesity / pathology
  • Vascular Endothelial Growth Factor B / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Vascular Endothelial Growth Factor B
  • Kdr protein, mouse
  • Vascular Endothelial Growth Factor Receptor-2