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

Marius R. Robciuc*, Riikka Kivela, Ian M. Williams, Jan Freark de Boer, Theo H. van Dijk, Harri Elamaa, Feven Tigistu-Sahle, Dmitry Molotkov, Veli-Matti Leppanen, Reijo Kakela, Lauri Eklund, David H. Wasserman, Albert K. Groen, Kari Alitalo

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

96 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)712-724
Number of pages13
JournalCell metabolism
Volume23
Issue number4
DOIs
Publication statusPublished - 12-Apr-2016

Keywords

  • ENDOTHELIAL GROWTH-FACTOR
  • FATTY-ACID UPTAKE
  • B-DEFICIENT MICE
  • VEGF-B
  • INSULIN-RESISTANCE
  • MYOCARDIAL-INFARCTION
  • SIGNAL-TRANSDUCTION
  • ANGIOGENESIS
  • RATS
  • INFLAMMATION

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