Computer‐Aided Functional Oligosaccharide Screening and the Regulatory Role in Lipid Metabolism

ABSTRACT This study investigated the lipid‐lowering effects and intervention mechanisms of structurally diverse functional oligosaccharides on non‐alcoholic fatty liver disease (NAFLD). By integrating computational tools such as molecular docking and molecular dynamics simulations (MDS), a comprehensive “in silico‐in vitro‐in vivo” tri‐dimensional screening and validation model was established that targeted the key lipid metabolism regulators peroxisome proliferator‐activated receptor alpha (PPARα) and peroxisome proliferator‐activated receptor gamma (PPARγ). This model successfully identified xylobiose and raffinose as candidate oligosaccharides with potential lipid‐lowering activity. Molecular docking was employed to elucidate the binding mechanisms between these oligosaccharides and their target proteins, highlighting the high structural stability of the PPARα‐ and PPARγ‐oligosaccharide complexes. Moreover, both the in vitro and in vivo models demonstrated that xylobiose and raffinose ameliorated hepatic lipid accumulation by inhibiting liver lipogenesis and modulating fatty acid oxidation to restore lipid homeostasis. The results demonstrated the reliability and robustness of the integrated computational‐experimental screening strategy, providing a transferable research paradigm for the targeted discovery of functional oligosaccharides and elucidating their underlying mechanisms.