Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis

Hoon Ki Sung, Kyung Oh Doh, Joe Eun Son, Jin Gyoon Park, Yunui Bae, Soojeong Choi, Seana Mary Lunney Nelson, Rebecca Cowling, Kristina Nagy, Iacovos P. Michael, Gou Young Koh, S. Lee Adamson, Tony Pawson, Andras Nagy

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

Vascular endothelial growth factor A (VEGF) is highly expressed in adipose tissue. Its role, however, has not been fully elucidated. Here, we reveal the metabolic role of adipose-VEGF by studying mice with deletion (VEGF AdΔ) or doxycycline-inducible overexpression of a VEGF transgene (VEGFAdTg) in the adipose tissue. VEGFAdΔ mice have reduced adipose vascular density and show adipose hypoxia, apoptosis, inflammation, and metabolic defects on a high-fat diet. In contrast, induction of VEGF expression in VEGFAdTg mice leads to increased adipose vasculature and reduced hypoxia. The latter changes are sufficient to counteract an established compromising effect of high-fat diet on the metabolism, indicating that metabolic misbalance is reversible by adipose vessel density increase. Our data clearly show the essential role of VEGF signaling for adequate adipose function. Besides revealing insights into the molecular mechanisms of obesity-related metabolic diseases, this study points to the therapeutic potential of increased adipose angiogenesis.

Original languageEnglish (US)
Pages (from-to)61-72
Number of pages12
JournalCell Metabolism
Volume17
Issue number1
DOIs
StatePublished - Jan 8 2013
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Sung, H. K., Doh, K. O., Son, J. E., Park, J. G., Bae, Y., Choi, S., Nelson, S. M. L., Cowling, R., Nagy, K., Michael, I. P., Koh, G. Y., Adamson, S. L., Pawson, T., & Nagy, A. (2013). Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis. Cell Metabolism, 17(1), 61-72. https://doi.org/10.1016/j.cmet.2012.12.010