Lycopene Alleviates Fatty Acid-Induced Oxidative Stress and Apoptosis in Bovine Mammary Epithelial Cells via the TFEB-Mediated Autophagy Signaling Pathway.

High concentrations of free fatty acids (FFA) during early lactation cause metabolic stress and oxidative damage in bovine mammary epithelial cells. This study explored the protective mechanism of lycopene (LYC), a natural antioxidant, against FFA-induced injury in the MAC-T cells. We found that 1.2 mM FFA induced oxidative stress, reactive oxygen species (ROS) accumulation, apoptosis, and impaired autophagy. LYC dose-dependently alleviated FFA-induced oxidative damage, restored autophagy flux, upregulated ATG5 autophagy-related 5 (ATG5), LC3-II, and transcription factor EB (TFEB), and downregulated p62, ROS, and apoptosis. Inhibition of autophagy abolished the protective effects of the LYC. Overexpression of TFEB mitigated FFA-induced dysfunction, while TFEB knockdown aggravated cell injury. These results demonstrate that LYC protects mammary epithelial cells from FFA-induced oxidative damage via regulating TFEB-mediated autophagy, suggesting its potential use in alleviating metabolic stress in periparturient dairy cows.