Combinatorial effect of Apigenin‐resveratrol on white adipocyte plasticity and trans‐differentiation for activating lipid metabolism

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.