Adipose vascular endothelial growth factor B is a major regulator of energy metabolism
Adipose vascular endothelial growth factor B is a major regulator of energy metabolism
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DOI：
10.1530/joe-19-0341
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发表时间：
2020-03-01
影响因子：
4
通讯作者：
Zheng, Yaowu
中科院分区：
文献类型：
--
作者：
Chen, Yang;Zhao, Mingyue;Zheng, Yaowu
过多的脂肪堆积会导致肥胖和许多疾病。先前的研究表明，VEGFB普遍敲除可诱导肥胖表型，包括白色脂肪组织扩张、棕色脂肪组织变白、脂肪积累增加和能量消耗减少。然而，vegf在脂肪组织中的作用尚不清楚。在本研究中，我们利用CRISPR/dCas9系统构建了脂肪特异性VEGFB抑制小鼠模型（VEGFB (AdipoDown)），并研究了VEGFB在脂肪发育和能量代谢中的作用。抑制VEGFB诱导脂肪组织结构和功能发生显著变化。Vegfb（AdipoDown）小鼠比其野生型幼崽体型更大，白色脂肪组织体积更大。脂肪特异性VEGFB抑制诱导脂肪组织向能量储存的白色脂肪的形态和功能转化。Vegfb（AdipoDown）脂肪组织的代谢过程发生了广泛的变化，包括碳水化合物代谢、脂质代谢、核苷酸代谢和氨基酸代谢。我们已经证明，脂肪的VEGFB抑制可以概括全身VEGFB敲除小鼠的大多数表型。有趣的是，脂肪组织中大约50%的VEGFB抑制几乎可以完全模仿VEGFB普遍缺失的效果，这表明脂肪VEGFB是能量代谢的主要调节因子，可能在预防和治疗肥胖中起重要作用。
Excessive fat accumulation causes obesity and many diseases. Previous study demonstrates VEGFB universal knockout induces obese phenotypes including expansion of white adipose tissue, whitening of brown adipose tissue, increase of fat accumulation and reduction in energy consumption. However, roles of VEGFB in adipose tissues are not clear. In this study, we have generated a mouse model with adipose-specific VEGFB repression using CRISPR/dCas9 system (Vegfb(AdipoDown)) and investigated the roles of VEGFB in adipose development and energy metabolism. VEGFB repression induced significant changes in adipose tissue structure and function. Vegfb(AdipoDown) mice have larger body sizes, larger volume of white adipose tissues than its wild type littermates. Adipose-specific VEGFB repression induced morphological and functional transformation of adipose tissues toward white adipose for energy storage. Metabolic processes are broadly changed in Vegfb(AdipoDown) adipose tissues including carbohydrate metabolism, lipid metabolism, nucleotide metabolism and amino acid metabolism. We have demonstrated that adipose VEGFB repression can recapitulate most of the phenotypes of the whole body VEGFB knockout mouse. Intriguingly, approximately 50% VEGFB repression in adipose tissues can almost completely mimic the effects of universal Vegfb deletion, suggesting adipose VEGFB is a major regulator of energy metabolism and may be important in prevention and treatment of obesity.