2. Academic Validation
  3. Free Fatty Acids Induce Apoptosis of Mammary Epithelial Cells of Ketotic Dairy Cows via the Mito-ROS/NLRP3 Signaling Pathway

Free Fatty Acids Induce Apoptosis of Mammary Epithelial Cells of Ketotic Dairy Cows via the Mito-ROS/NLRP3 Signaling Pathway

  • J Agric Food Chem. 2023 Aug 30;71(34):12645-12656. doi: 10.1021/acs.jafc.3c02090.
Renxu Chang 1 2 3,  Hongdou Jia 2,  Zhihao Dong 2,  Qiushi Xu 2,  Lei Liu 1,  Zolzaya Majigsuren 4,  Tugsjargal Batbaatar 5,  Chuang Xu 3,  Qing Yang 1,  Xudong Sun 2
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China.
  • 2 Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China.
  • 3 College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
  • 4 Institute of Veterinary Medicine, Mongolian University of Life Sciences, Zaisan, Ulaanbaatar 17024, Mongolia.
  • 5 State Central Veterinary Laboratory, P. O. Box 53/33, Zaisan, Ulaanbaatar 210153, Mongolia.
PMID: 37585786 DOI: 10.1021/acs.jafc.3c02090
Abstract

Early lactation increases metabolic stress in ketotic dairy cows, leading to mitochondrial damage, Apoptosis, and inflammatory response in mammary epithelial cells. The pyrin domain 3 (NLRP3) pathway involving the mitochondrial Reactive Oxygen Species (Mito-ROS)-induced nucleotide-binding oligomerization domain-like receptor has been recognized as a key mechanism in this inflammatory response and cell Apoptosis. This study aimed to elucidate the underlying regulatory mechanism of Mito-ROS-NLRP3 pathway-mediated mammary epithelial cell Apoptosis in dairy cows with ketosis. Mitochondrial damage and cellular apoptotic program and NLRP3 inflammasome activation were observed in the mammary gland of ketotic cows. Similar damage was detected in MAC-T cells treated with exogenous fatty acids (FFAs). However, NLRP3 Inhibitor MCC950 pretreatment or Mito-ROS scavenging by MitoTEMPO attenuated Apoptosis in FFA-induced MAC-T cells by inhibiting the NLRP3 inflammasome pathway. These findings reveal that the Mito-ROS-NLRP3 pathway activation is a potent mechanism underlying mammary epithelial cell Apoptosis in response to metabolic stress in ketotic dairy cows, which further contributes to reduced milk yield.

Keywords

Mito-ROS; NLRP3; apoptosis; bovine mammary epithelial cells.

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