Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, AustraliaLaboratory for Ageing Research, School of Medical Sciences, UNSW Australia, New South Wales, Australia.
Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
Diabetes. 2014 Aug;63(8):2656-67. doi: 10.2337/db13-1665. Epub 2014 Apr 2.
The vascular endothelial growth factor (VEGF) family of cytokines are important regulators of angiogenesis that have emerged as important targets for the treatment of obesity. While serum VEGF levels rise during obesity, recent studies using genetic models provide conflicting evidence as to whether VEGF prevents or accelerates metabolic dysfunction during obesity. In the current study, we sought to identify the effects of VEGF-A neutralization on parameters of glucose metabolism and insulin action in a dietary mouse model of obesity. Within only 72 h of administration of the VEGF-A-neutralizing monoclonal antibody B.20-4.1, we observed almost complete reversal of high-fat diet-induced insulin resistance principally due to improved insulin sensitivity in the liver and in adipose tissue. These effects were independent of changes in whole-body adiposity or insulin signaling. These findings show an important and unexpected role for VEGF in liver insulin resistance, opening up a potentially novel therapeutic avenue for obesity-related metabolic disease.
血管内皮生长因子（VEGF）细胞因子家族是血管生成的重要调节剂，已成为肥胖症治疗的重要靶点。虽然肥胖期间血清 VEGF 水平升高，但最近使用遗传模型的研究对 VEGF 是否预防或加速肥胖期间的代谢功能障碍提供了相互矛盾的证据。在本研究中，我们试图确定 VEGF-A 中和在肥胖饮食小鼠模型中对葡萄糖代谢和胰岛素作用参数的影响。在给予 VEGF-A 中和单克隆抗体 B.20-4.1 的仅 72 小时内，我们观察到高脂肪饮食诱导的胰岛素抵抗几乎完全逆转，主要是由于肝脏和脂肪组织中胰岛素敏感性的提高。这些作用与全身肥胖或胰岛素信号的变化无关。这些发现表明 VEGF 在肝脏胰岛素抵抗中具有重要且意外的作用，为肥胖相关代谢性疾病开辟了一条潜在的新的治疗途径。
