@article{Chang2026, 
author = {Renxu Chang and Yuanyuan Chen and Xinyi Xu and Hongdou Jia and John Mauck and Juan J. Loor and Yehoshav A. Ben Meir and Qiushi Xu and Xudong Sun and Chuang Xu},
title = {Free fatty acids induce apoptosis in mammary epithelial cells from ketotic dairy cows via endoplasmic reticulum stress},
year = {2026},
journal = {Journal of Integrative Agriculture (JIA)},
volume = {25},
number = {5},
pages = {2014-2027},
keywords = {ketosis, bovine mammary epithelial cells, ER stress, apoptosis},
url = {https://www.sciopen.com/article/10.1016/j.jia.2024.12.023},
doi = {10.1016/j.jia.2024.12.023},
abstract = {The mammary glands of dairy cows with ketosis face unique challenges, including the supraphysiological circulating concentrations of free fatty acids (FFA) and apoptosis of epithelial cells. The fact that endoplasmic reticulum (ER) stress and apoptosis are closely related processes (at least in nonruminants) suggests that mechanisms of metabolic stress-induced apoptosis in bovine mammary epithelial cells may involve the ER stress pathway. The objective of this study was to investigate (1) the status of the ER stress pathway in mammary gland of dairy cows with ketosis, and (2) the role of ER stress in the apoptosis of bovine mammary epithelial cells challenged with high concentrations of FFA. Ketosis or exogenous FFA activated the ER stress pathway in the mammary gland of dairy cows or MAC-T cells. Pretreatment with the ER stress activator Tunicamycin (Tun) aggravated ER stress and apoptosis in MAC-T cells induced by FFA. However, ER stress inhibitor Tauroursodeoxycholate (TUDCA) attenuated ER stress induced by FFA and also attenuated the apoptosis in MAC-T cells. In conclusion, the data confirmed that FFA induced apoptosis of bovine mammary epithelial cells in dairy cows with ketosis via ER stress signaling. Thus, timely resolution of ER stress may help counteract the negative effects of ketosis on the mammary gland.}
}