Abstract：
Inducing browning in white adipocytes has emerged as a promising therapeutic approach for addressing obesity. Bioactive that modulate the WAT microenvironment to induce trans browning in white adipocytes have been explored as a strategy to control unregulated lipid storage. However, relying on a single bioactive for modulating lipid metabolism has proven insufficient in obese individuals during human trials, because these compounds primarily activate a single biochemical pathway in promoting browning. Consequently, there is a growing emphasis on targeting multiple pathways to ensure a safe and effective browning process. The present study investigated the combinatorial effect of bioactives namely Apigenin and Resveratrol for activating multiple pathways for effective trans-browning of white adipocytes. The combination was seen to promote the browning more effectively than the single bioactive, as the combination simultaneously activated multiple signaling pathways to induce angiogenesis-mediated browning in primary white adipocytes isolated from obese mice. Activation of PI3K signaling via estrogen receptor-α-dependent pathway resulted in simultaneous activation of angiogenesis and trans browning in white adipocytes. The study provides valuable insights into the potential use of bioactives in combination with therapeutic intervention to improve the overall health of obese subjects by enhancing lipid metabolism by activating trans-differentiation of white adipocytes.
摘要：
诱导白色脂肪细胞褐变已成为解决肥胖的有希望的治疗方法。已经探索了调节WAT微环境以诱导白色脂肪细胞中反式褐变的生物活性作为控制未调节的脂质储存的策略。然而,在人体试验中，肥胖个体依靠单一生物活性物质来调节脂质代谢已被证明是不够的，因为这些化合物主要激活促进褐变的单一生化途径。因此,人们越来越重视针对多种途径，以确保安全和有效的褐变过程。本研究调查了生物活性物质即芹菜素和白藜芦醇的联合作用,以激活白色脂肪细胞的有效反式褐变的多种途径。该组合被认为比单一生物活性物质更有效地促进褐变，作为组合同时激活多个信号通路，以诱导从肥胖小鼠分离的原代白色脂肪细胞中血管生成介导的褐变。通过雌激素受体α依赖性途径激活PI3K信号导致白色脂肪细胞中血管生成和反式褐变的同时激活。该研究提供了有关生物活性物质与治疗干预相结合的潜在用途的有价值的见解，以通过激活白色脂肪细胞的转分化来增强脂质代谢来改善肥胖受试者的整体健康。
