Blockade of VEGFR2 and not VEGFR1 can limit diet-induced fat tissue expansion: Role of local versus bone marrow-derived endothelial cells

Joshua Tam, Dan G. Duda, Jean Y. Perentes, Rehan S. Quadri, Dai Fukumura, Rakesh K. Jain

Research output: Contribution to journalArticlepeer-review

Abstract

Background: We investigated if new vessel formation in fat involves the contribution of local tissue-derived endothelial cells (i.e., angiogenesis) or bone marrow-derived cells (BMDCs, i.e. vasculogenesis) and if antiangiogenic treatment by blockade of vascular endothelial growth factor (VEGF) receptors can prevent diet-induced obesity (DIO). Methodology/Principal Findings: We performed restorative bone marrow transplantation into wild-type mice using transgenic mice expressing green fluorescent protein (GFP) constitutively (driven by β-actin promoter) or selectively in endothelial cells (under Tie2 promoter activation) as donors. The presence of donor BMDCs in recipient mice was investigated in fat tissue vessels after DIO using in vivo and ex vivo fluorescence microscopy. We investigated the roles of VEGF receptors 1 and 2 (VEGFR1/VEGFR2) by inducing DIO in mice and treating them with blocking monoclonal antibodies. We found only marginal (less than 1%) incorporation of BMDCs in fat vessels during DIO. When angiogenesis was inhibited by blocking VEGFR2 in mice with DIO, treated mice had significantly lower body weights than control animals. In contrast, blocking VEGFR1 had no discernable effect on the weight gain during DIO. Conclusions/Significance: Formation of new vessels in fat tissues during DIO is largely due to angiogenesis rather than de novo vasculogenesis. Antiangiogenic treatment by blockade of VEGFR2 but not VEGFR1 may limit adipose tissue expansion.

Original languageEnglish (US)
Article numbere4974
JournalPloS one
Volume4
Issue number3
DOIs
StatePublished - Mar 31 2009
Externally publishedYes

ASJC Scopus subject areas

  • General

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