Molecular Mechanisms Underlying the Proliferative Effects of ω-3 Polyunsaturated Fatty Acids on Intestinal Epithelial Cells

The proliferation of small intestinal epithelial cells is fundamental to intestinal development and barrier function maintenance in infants and young children. To investigate the effects and mechanisms of ω-3 polyunsaturated fatty acids (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)), commonly used in infant formula, on this process, this study employed the rat intestinal epithelial cell line 6 (IEC-6) as a model. After DHA and EPA treatment at different combinations of concentration (1, 10, 50, 100 μmol/L) and duration 12, 24, 36, 48 h, cell viability was assessed using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays, and the mRNA and protein expression of key molecules involved in the Wnt/β-catenin signaling pathways were analyzed via real-time quantitative polymerase chain reaction and Western blot. The results showed that both DHA and EPA significantly promoted the proliferation of IEC-6 cells, with optimal concentrations of 100 and 10 μmol/L, respectively, and an optimal treatment duration of 24 h. Specifically, treatment with 100 μmol/L DHA and 10 μmol/L EPA for 24 h increased cell viability by nearly 4- and 3.5-fold compared to the control group (P < 0.001), respectively. Both DHA and EPA activated the Wnt/β-catenin signaling pathway, significantly upregulating the mRNA and protein expression of cell proliferation-related genes such as cyclin D1 and β-catenin (P < 0.05, P < 0.01, or P < 0.001). These findings indicate that DHA and EPA enhance intestinal epithelial cell proliferation by activating the Wnt signaling pathway.