Elsevier

Molecular Metabolism

Volume 3, Issue 4, July 2014, Pages 474-483
Molecular Metabolism

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

https://doi.org/10.1016/j.molmet.2014.03.010Get rights and content
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Abstract

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 in vivo. 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.

Keywords

VEGF-A
BAT
Cold tolerance
Energy expenditure

Abbreviations

BAT
brown adipose tissue
WAT
white adipose tissue
UCP1
uncoupling protein1
Dox
doxycycline
HFD
high-fat diet
PGC-1α
PPARγ co-activator-1α
OCR
oxygen consumption rate
OGTT
oral glucose tolerance test
HIF1
hypoxia-induced factor1

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