Journal
MOLECULAR METABOLISM
Volume 3, Issue 4, Pages 474-483Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molmet.2014.03.010
Keywords
VEGF-A; BAT; Cold tolerance; Energy expenditure
Categories
Funding
- NIDDK NIH HHS [P01 DK088761, R01 DK055758, R00 DK094973, R01 DK099110] Funding Source: Medline
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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-1 alpha 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. (C) 2014 The Authors. Published by Elsevier GmbH.
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