Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Mol Metab. 2014 Apr 5;3(4):474-83. doi: 10.1016/j.molmet.2014.03.010. eCollection 2014 Jul.
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.
我们最近报道称，血管内皮生长因子 A（VEGF-A）在白色脂肪组织（WAT）中的局部过表达可预防饮食诱导的肥胖和代谢功能障碍。观察到 VEGF-A 可在 WAT 中诱导出“棕色脂肪组织（BAT）样”表型，这促使我们进一步探索 VEGF-A 在 BAT 中的直接功能。我们利用强力霉素（Dox）诱导的、棕色脂肪细胞特异性 VEGF-A 转基因过表达模型，在体内评估了 VEGF-A 在 BAT 中的直接作用。我们发现，BAT 特异性 VEGF-A 表达增加了血管生成，并上调了 BAT 中 UCP1 和 PGC-1α 的表达。结果，转基因小鼠在慢性寒冷暴露期间表现出增加的产热。在饮食诱导的肥胖小鼠中，局部在 BAT 中引入 VEGF-A 可挽救毛细血管稀疏，改善棕色脂肪细胞功能障碍，并改善高脂肪饮食挑战引起的葡萄糖和脂质代谢的有害影响。这些结果表明 VEGF-A 在 BAT 的激活和扩张中具有直接的积极作用。
