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 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 language | English (US) |
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Pages (from-to) | 474-483 |
Number of pages | 10 |
Journal | Molecular Metabolism |
Volume | 3 |
Issue number | 4 |
DOIs | |
State | Published - Jul 2014 |
Keywords
- BAT
- Cold tolerance
- Energy expenditure
- VEGF-A
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology