Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure

Kai Sun, Christine M. Kusminski, Kate Luby-Phelps, Stephen B. Spurgin, Yu A. An, Qiong A. Wang, William L. Holland, Philipp E. Scherer

Research output: Contribution to journalArticlepeer-review

114 Scopus citations


We recently reported that local overexpression of VEGF-A in white adipose tissue (WAT) protects against diet-induced obesity and metabolic dysfunction. The observation that VEGF-A induces a "brown adipose tissue (BAT)-like" phenotype in WAT prompted us to further explore the direct function of VEGF-A in BAT. We utilized a doxycycline (Dox)-inducible, brown adipocyte-specific VEGF-A transgenic overexpression model to assess direct effects of VEGF-A in BAT invivo. We observed that BAT-specific VEGF-A expression increases vascularization and up-regulates expression of both UCP1 and PGC-1α in BAT. As a result, the transgenic mice show increased thermogenesis during chronic cold exposure. In diet-induced obese mice, introducing VEGF-A locally in BAT rescues capillary rarefaction, ameliorates brown adipocyte dysfunction, and improves deleterious effects on glucose and lipid metabolism caused by a high-fat diet challenge. These results demonstrate a direct positive role of VEGF-A in the activation and expansion of BAT.

Original languageEnglish (US)
Pages (from-to)474-483
Number of pages10
JournalMolecular Metabolism
Issue number4
StatePublished - Jul 2014


  • BAT
  • Cold tolerance
  • Energy expenditure
  • VEGF-A

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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