Elucidating the molecular mechanism of myofibrillar protein-luteolin affecting lipid accumulation and oxidative stress in HepG2 cells

The luteolin (Lut) binding with myofibrillar protein (MP) can enhance the functionality of proteins, having the potential to ameliorate obesity in the form of dietary intervention. Our previous research unveiled the <em>in vitro</em>&nbsp;cell viability and antioxidant properties of the MP-derived and Lut-containing multicomponent peptides (MDLPs). This study aimed to further investigate the effect of MDLPs intervention and downstream effects on lipid metabolism using integrated physiological and multi-omics approaches. The results demonstrated that MDLPs significantly ameliorated steatosis and systemic oxidative stress in HepG2 cells induced by a high-fat (HF) reagent. Combining metabolomic and transcriptomic analysis indicated that PPAR, FoxO, and amino acids metabolism signaling pathways played pivotal roles in response to the MDLPs intervention, primarily through upregulating PPARα, PPARγ, FOXO1, and PLIN4. The abundance of potential disease biomarkers (4-hydroxynonenal and hydroxylinoleic acid) were enhanced. The outcomes of this research provide the theoretical basis for the formulation of novel meat products with anti-obesity activity.