Thermogenic activation via trans-and de novo browning of white adipocytes is a promising strategy to accelerate lipid metabolism for regulating obesity-related disorders. In this study, we investigated the intricate interplay between angiogenic regulation and browning in white adipocytes using the bioactive compound, resveratrol (Rsv). Rsv has previously been documented for its regulatory influence on the trans and de novo browning of white adipocytes. Our findings revealed that concurrent activation of angiogenesis is prerequisite for inducing browning within the microenvironment of white adipocytes when exposed to browning activators. Additionally, we observed a significant browning effect on white adipocytes when the local adipose tissue environment was prompted to undergo angiogenesis, notably facilitated by a proangiogenic molecule known as Vascular endothelial growth factor (VEGF). Intriguingly, this effect was reversed when angiogenesis was inhibited by treatment with the antiangiogenic agent thalidomide. Furthermore, the study revealed the role of VEGF in paracrine activation of white adipocytes resulting in the induction of browning in both 3T3-L1 cell lines and primary mouse white adipocytes. The cross-talk between angiogenesis and browning was found to be initiated via the transcriptional activation of Estrogen receptor α (ERα) triggering the VEGF/VEGFR2 signaling pathway leading to browning and a reconfiguration of lipid metabolism within adipocytes. In conclusion, this study sheds light on the intricate cross-talk between angiogenesis and browning of white adipocytes. Notably, the findings underscore the reciprocal relationship between these processes, wherein inhibition of one process exerts discernible effects on the other.

通过白色脂肪细胞的反式和从头褐变产生的生热激活是加速脂质代谢以调节肥胖相关疾病的一种有前途的策略。在这项研究中，我们使用生物活性化合物白藜芦醇（Rsv）研究了白色脂肪细胞中血管生成调节和褐变之间复杂的相互作用。Rsv 先前已被证明其对白色脂肪细胞的反式和从头褐变的调节影响。我们的研究结果表明，当暴露于褐变激活剂时，血管生成的同时激活是在白色脂肪细胞的微环境中诱导褐变的先决条件。此外，我们观察到当局部脂肪组织环境促进血管生成时，白色脂肪细胞出现显着的褐变效应，特别是由称为血管内皮生长因子（VEGF）的促血管生成分子促进。有趣的是，当用抗血管生成剂沙利度胺治疗抑制血管生成时，这种效应被逆转。此外，该研究揭示了 VEGF 在白色脂肪细胞旁分泌激活中的作用，导致 3T3-L1 细胞系和原代小鼠白色脂肪细胞褐变。研究发现，血管生成和褐变之间的相互作用是通过雌激素受体 α (ERα) 的转录激活引发的，从而触发 VEGF/VEGFR2信号通路，从而导致褐变和脂肪细胞内脂质代谢的重新配置。总之，这项研究揭示了血管生成和白色脂肪细胞褐变之间复杂的相互作用。值得注意的是，这些发现强调了这些过程之间的相互关系，其中一个过程的抑制会对另一个过程产生明显的影响。