Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues
Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues
复制标题
DOI：
10.1073/pnas.1415825111
复制
发表时间：
2014-10-14
影响因子：
11.1
通讯作者：
Cao, Yihai
中科院分区：
文献类型：
--
作者：
Honek, Jennifer;Seki, Takahiro;Cao, Yihai
与年龄相关的肥胖和胰岛素抵抗的潜在机制通常是未知的。在这里，我们报告年龄相关的脂肪血管的变化显着调制的脂肪量，脂肪细胞的功能，血脂成分和胰岛素敏感性。值得注意的是，VEGF表达水平在各种白色脂肪组织（WAT）经历了不间断的变化，在不同的年龄人群。抗VEGF和抗VEGF受体2治疗在不同年龄人群中显示出血管消退的显著变化，中年小鼠表现出适度的敏感性。有趣的是，抗VEGF治疗对不同年龄人群中的WAT脂肪细胞大小产生相反的影响，并影响棕色脂肪组织中的血管密度和脂肪细胞大小。与血管和脂肪细胞大小的变化一致，抗VEGF治疗增加了年轻和老年小鼠的胰岛素敏感性，但对中年组没有影响。令人惊讶的是，抗VEGF治疗显著改善了喂食高脂饮食的中年肥胖小鼠的胰岛素敏感性。我们的研究结果表明，脂肪血管显示不同年龄人群的抗VEGF治疗的差异反应，并具有治疗肥胖症和糖尿病与抗VEGF为基础的抗血管生成药物的治疗意义。
Mechanisms underlying age-related obesity and insulin resistance are generally unknown. Here, we report age-related adipose vascular changes markedly modulated fat mass, adipocyte functions, blood lipid composition, and insulin sensitivity. Notably, VEGF expression levels in various white adipose tissues (WATs) underwent changes uninterruptedly in different age populations. Anti-VEGF and anti-VEGF receptor 2 treatment in different age populations showed marked variations of vascular regression, with midaged mice exhibiting modest sensitivity. Interestingly, anti-VEGF treatment produced opposing effects on WAT adipocyte sizes in different age populations and affected vascular density and adipocyte sizes in brown adipose tissue. Consistent with changes of vasculatures and adipocyte sizes, anti-VEGF treatment increased insulin sensitivity in young and old mice but had no effects in the midaged group. Surprisingly, anti-VEGF treatment significantly improved insulin sensitivity in midaged obese mice fed a high-fat diet. Our findings demonstrate that adipose vasculatures show differential responses to anti-VEGF treatment in various age populations and have therapeutic implications for treatment of obesity and diabetes with anti-VEGF-based antiangiogenic drugs.