NRF2-CD36 Axis-Mediated Oleic Acid-Induced Milk Fat Production in Dairy Cow Mammary Epithelial Cells

Oleic acid (OA)-enriched diet significantly enhances CD36 expression and promotes milk fat production in the mammary gland. However, the mechanisms by which OA upregulates this process are unknown. Here, GC-MS analysis and molecular docking were used to assess OA-CD36 binding, while gene expression and ChIP assays clarified the OA-mediated regulation of CD36 and milk fat synthesis. The results showed that CD36 is highly expressed in the lactating mammary tissues of dairy cows and positively regulates milk fat production. OA enters dairy cow mammary epithelial cells via direct binding to CD36. OA stimulation elevates the CD36 expression and translocation. ChIP assays confirmed CD36 as a target gene of NRF2. OA also enhances NRF2 expression and nuclear translocation, which in turn upregulates CD36 expression and function. This study elucidates the NRF2–CD36 axis as a regulator of OA-driven milk fat synthesis in mammary tissue, offering practical value for dairy industry nutritional strategies.