Minerva Foundation Institute for Medical Research, Helsinki, Finland, and Department of Anatomy, Faculty of Medicine, University of Helsinki, Finland.
Minerva Foundation Institute for Medical Research, Helsinki, Finland, and Department of Anatomy, Faculty of Medicine, University of Helsinki, Finland.
Biochem Pharmacol. 2024 Apr;222:116081. doi: 10.1016/j.bcp.2024.116081. Epub 2024 Feb 24.
Adipose tissue (AT) expansion through hyperplasia or hypertrophy requires vascular remodeling that involves angiogenesis. There is quite some evidence that obese white AT (WAT) displays altered vasculature. Some studies suggest that this is associated with hypoxia, which is thought to play a role in inducing inflammatory activation of the excessively expanding WAT. Increasing evidence, based on genetic manipulations or treatments with inhibitory or activator pharmaceuticals, demonstrates that AT angiogenesis is crucial for AT metabolic function, and thereby for whole body metabolism and metabolic health. Despite some contradiction between studies, disturbance of WAT angiogenesis in obesity could be an important factor driving WAT dysfunction and the comorbidities of obesity. Endothelial cells (ECs) contribute to healthy WAT metabolism via transport of fatty acids and other plasma components, secretory signaling molecules, and extracellular vesicles (EVs). This communication is crucial for adipocyte metabolism and underscores the key role that the AT endothelium plays in systemic energy homeostasis and healthy metabolism. Adipocytes communicate towards the neighboring endothelium through several mechanisms. The pro-inflammatory status of hypertrophic adipocytes in obesity is reflected in ECs activation, which promotes chronic inflammation. On the other hand, adiponectin secreted by the adipocytes is important for healthy endothelial function, and adipocytes also secrete other pro- or anti-angiogenic effector molecules and a wealth of EVs - however, their detailed roles in signaling towards the endothelium are yet poorly understood. To conclude, targeting AT angiogenesis and promoting the healthy communication between adipocytes and ECs represent potentially promising strategies to treat obesity and its comorbidities.
脂肪组织（AT）通过增生或肥大扩张需要血管重塑，包括血管生成。有相当多的证据表明，肥胖的白色脂肪组织（WAT）显示出改变的脉管系统。一些研究表明，这与缺氧有关，缺氧被认为在诱导过度扩张的 WAT 的炎症激活中起作用。越来越多的证据表明，基于遗传操作或使用抑制或激活药物的治疗，AT 血管生成对于 AT 代谢功能至关重要，从而对于全身代谢和代谢健康至关重要。尽管研究之间存在一些矛盾，但肥胖症中 WAT 血管生成的紊乱可能是驱动 WAT 功能障碍和肥胖合并症的重要因素。内皮细胞（ECs）通过运输脂肪酸和其他血浆成分、分泌信号分子和细胞外囊泡（EVs）为健康的 WAT 代谢做出贡献。这种通讯对于脂肪细胞代谢至关重要，强调了 AT 内皮在全身能量平衡和健康代谢中的关键作用。脂肪细胞通过几种机制向邻近的内皮细胞传递信号。肥胖症中肥大脂肪细胞的促炎状态反映在 ECs 的激活上，这促进了慢性炎症。另一方面，脂肪细胞分泌的脂联素对于健康的内皮功能很重要，脂肪细胞还分泌其他促血管生成或抗血管生成效应分子和丰富的 EVs-然而，它们在向内皮细胞发出信号方面的详细作用仍知之甚少。总之，靶向 AT 血管生成和促进脂肪细胞和 ECs 之间的健康通讯代表了治疗肥胖症及其合并症的潜在有前途的策略。
