Luteolin-Loaded WPI/Pueraria lobata Amylopectin Composite Gel Improves Adipocyte Thermogenesis and Insulin Sensitivity

Adipose tissue metabolic dysfunction plays a central role in the development of obesity and related metabolic disease. Luteolin is a natural flavonoid with antioxidant, anti-inflammatory, antidiabetic, and antiobesity activities, while it is limited by poor solubility, bioavailability, and stability. This study developed a whey protein isolate (WPI)– Pueraria lobata amylopectin (PLA) composite gel, characterized by a dense 3D network and enhanced mechanical strength. The WPI-PLA gel efficiently encapsulated luteolin in a stable amorphous form and exhibited uniform particle size and excellent colloidal stability. This encapsulation improved the light, storage, and thermal stabilities of luteolin; enhanced its antioxidant activity due to improved dispersion; and enabled its preferential intestinal release. Encapsulated luteolin promoted the expression of thermogenic genes UCP1, Pgc - 1α, Prdm16, and Cidea and protein levels of UCP1 and catalase in brown-differentiated C3H10T1/2 cells and inhibited the expression of lipopolysaccharide-induced inflammatory cytokines Il-6, Tnf - α, and Il - 1β in RAW264.7 macrophages. In differentiated white 3T3-L1 adipocytes, WPI-LU-PLA restored insulin sensitivity impaired by macrophage-conditioned medium. This reversal was indicated by the enhanced expression of the insulin sensitivity-related genes GLUT4 and Irs1, along with increases in GLUT4 and p-Akt protein levels. In conclusion, the WPI-PLA composite gel enhances the stability, bioaccessibility, and bioactivity of luteolin, suggesting potential for functional foods targeting metabolic dysfunction in adipose tissues.