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High levels of fatty acids inhibit β-casein synthesis through suppression of the JAK2/STAT5 and mTOR signaling pathways in mammary epithelial cells of cows with clinical ketosis

  • Xin Shu (a1), Zhiyuan Fang (a1), Yuan Guan (a2), Xiying Chen (a1), Juan J. Loor (a3), Hongdou Jia (a1), Jihong Dong (a1), Yazhe Wang (a1), Rankun Zuo (a4), Guowen Liu (a1), Xiaobing Li (a1) and Xinwei Li (a1)...


Ketosis is a metabolic disease of dairy cows often characterized by high concentrations of ketone bodies and fatty acids, but low milk protein and milk production. The Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) and the mechanistic target of rapamycin (mTOR) signaling pathways are central for the regulation of milk protein synthesis. The effect of high levels of fatty acids on these pathways and β-casein synthesis are unknown in dairy cows with clinical ketosis. Mammary gland tissue and blood samples were collected from healthy (n = 15) and clinically-ketotic (n = 15) cows. In addition, bovine mammary epithelial cells (BMEC) were treated with fatty acids, methionine (Met) or prolactin (PRL), respectively. In vivo, the serum concentration of fatty acids was greater (P > 0.05) and the percentage of milk protein (P > 0.05) was lower in cows with clinical ketosis. The JAK2-STAT5 and mTOR signaling pathways were inhibited and the abundance of β-casein was lower in mammary tissue of cows with clinical ketosis (P > 0.05). In vitro, high levels of fatty acids inhibited the JAK2-STAT5 and mTOR signaling pathways (P > 0.05) and further decreased the β-casein synthesis (P > 0.05) in BMEC. Methionine or PRL treatment, as positive regulators, activated the JAK2-STAT5 and mTOR signaling pathways to increase the β-casein synthesis. Importantly, the high concentration of fatty acids attenuated the positive effect of Met or PRL on mTOR, JAK2-STAT5 pathways and the abundance of β-casein (P > 0.05). Overall, these data indicate that the high concentrations of fatty acids that reach the mammary cells during clinical ketosis inhibit mTOR and JAK2-STAT5 signaling pathways, and further suppress β-casein synthesis.


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Author for correspondence: Xinwei Li, Email:


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These authors contributed equally to this study.



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High levels of fatty acids inhibit β-casein synthesis through suppression of the JAK2/STAT5 and mTOR signaling pathways in mammary epithelial cells of cows with clinical ketosis

  • Xin Shu (a1), Zhiyuan Fang (a1), Yuan Guan (a2), Xiying Chen (a1), Juan J. Loor (a3), Hongdou Jia (a1), Jihong Dong (a1), Yazhe Wang (a1), Rankun Zuo (a4), Guowen Liu (a1), Xiaobing Li (a1) and Xinwei Li (a1)...


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