Wang Chenguang, Wu Yalan, Li Yangxian, Zhang Yang, Fung Yee Lok, Tong Ka Kui, Lau Chi Wai, Xiang Li, Kwan Kin Ming, You Li-Ru, Huang Yu, Tian Xiao Yu
School of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.
School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
iScience. 2023 Feb 25;26(3):106272. doi: 10.1016/j.isci.2023.106272. eCollection 2023 Mar 17.
Beige adipocytes are thermogenic with high expression of uncoupling protein 1 in the white adipose tissue (WAT), accompanied by angiogenesis. Previous studies showed that is important for angiogenesis. Here we studied whether endothelial -mediated angiogenesis is involved in WAT beiging. Inducible knockout of endothelial cell (EC) selective ( ) was achieved by using the and mice. Beige fat induction achieved by cold or adrenergic agonist, and angiogenesis were attenuated in WAT of mice, with the less proliferation of ECs and adipogenic precursors. RNA sequencing of human ECs showed that Smad4 is involved in angiogenesis-related pathways. Knockdown of SMAD4 attenuated the upregulation of VEGFA, PDGFA, and angiogenesis . Treatment of human ECs with palmitic acid-induced Smad1/5 phosphorylation and the upregulation of core endothelial genes. Our study shows that endothelial Smad4 is involved in WAT beiging through angiogenesis and the expansion of adipose precursors into beige adipocytes.
米色脂肪细胞具有产热功能，白色脂肪组织（WAT）中的解偶联蛋白1表达量高，且伴有血管生成。先前的研究表明，[此处原文缺失关键内容]对血管生成很重要。在此，我们研究了内皮细胞介导的血管生成是否参与白色脂肪组织米色化过程。通过使用[此处原文缺失关键内容]和[此处原文缺失关键内容]小鼠实现了内皮细胞（EC）选择性[此处原文缺失关键内容]的诱导性敲除。通过寒冷或肾上腺素能激动剂诱导米色脂肪生成，[此处原文缺失关键内容]小鼠的白色脂肪组织中的血管生成减弱，内皮细胞和成脂前体细胞的增殖减少。对人内皮细胞进行RNA测序表明，Smad4参与血管生成相关途径。敲低SMAD4可减弱VEGFA、PDGFA的上调以及血管生成[此处原文缺失关键内容]。用棕榈酸处理人内皮细胞可诱导Smad1/5磷酸化以及核心内皮基因的上调。我们的研究表明，内皮细胞中的Smad4通过血管生成以及脂肪前体细胞向米色脂肪细胞的分化参与白色脂肪组织米色化过程。
