Nuciferine Ameliorates Nonesterified Fatty Acid-Induced Bovine Mammary Epithelial Cell Lipid Accumulation, Apoptosis, and Impaired Migration via Activating LKB1/AMPK Signaling Pathway.
Nuciferine Ameliorates Nonesterified Fatty Acid-Induced Bovine Mammary Epithelial Cell Lipid Accumulation, Apoptosis, and Impaired Migration via Activating LKB1/AMPK Signaling Pathway.
复制标题
荷叶碱通过激活LKB 1/AMPK信号通路改善非酯化脂肪酸诱导的牛乳腺上皮细胞脂质蓄积、凋亡和迁移受损。
DOI：
10.1021/acs.jafc.2c06133
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发表时间：
2022-12
影响因子：
6.1
通讯作者：
Jinxia Li;Chenchen Zhao;Menglin Liu;Linfang Chen;Yiwei Zhu;W. Gao;Xiliang Du;Yuxiang Song
中科院分区：
文献类型：
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作者：
Jinxia Li;Chenchen Zhao;Menglin Liu;Linfang Chen;Yiwei Zhu;W. Gao;Xiliang Du;Yuxiang Song
血液中高浓度的非酯化脂肪酸(NEFAs)会引起各种代谢紊乱，并与奶牛的乳房组织损伤和产奶量减少有关。荷花碱是莲叶中发现的一种生物碱，具有纠正脂代谢紊乱和脂毒性的巨大潜力。在这项研究中，我们评估了过量的NEFA对牛乳腺上皮细胞(BMECs)的脂毒性，并探讨了荷叶碱是否减轻了NEFA诱导的脂毒性及其分子机制。我们发现，过量的NEFA(1.2mM和2.4mM)可导致bMEC脂质堆积、细胞凋亡和迁移能力受损，而荷包牡丹碱可以改善这些紊乱，表现为甘油三酯含量、SREBP-1c蛋白丰度、细胞质细胞色素c和裂解的caspase-3，增加PPARα的蛋白丰度和迁移能力。荷包牡丹碱可逆转NEFA对LKB1/AMPK信号通路的抑制作用，且荷包牡丹碱对NEFA引起的脂毒性的保护作用可被AMPK抑制剂桃仁吗啡所阻断。此外，转染LKB1 siRNA(si-LKB1)后，荷叶碱对AMPK的激活作用基本消失。总之，荷包牡丹碱可通过激活LKB1/AMPK信号通路，保护bMECs免受NEFA诱导的过度脂质蓄积、细胞凋亡和迁移障碍的影响。
High blood concentrations of nonesterified fatty acids (NEFAs) provoke various metabolic disorders and are associated with mammary tissue injury and decreased milk production in dairy cows. Nuciferine, an alkaloid found in Nelumbo nucifera leaves, has great potential for correcting lipid metabolism derangements and lipotoxicity. In this study, we evaluated the lipotoxicity induced by excessive NEFA in bovine mammary epithelial cells (bMECs) and investigated whether nuciferine alleviates NEFA-induced lipotoxicity and the underlying molecular mechanisms. We found that excessive NEFA (1.2 and 2.4 mM) induced lipid accumulation, apoptosis, and migration ability impairment in bMECs, whereas nuciferine could ameliorate these disarrangements, as indicated by decreasing triglyceride content, protein abundance of SREBP-1c, cytoplasmic cytochrome c, and cleaved caspase-3 and increasing protein abundance of PPARα and migration ability. Moreover, nuciferine could reverse NEFA-induced LKB1/AMPK signaling inhibition, and the protective effect of nuciferine on lipotoxicity caused by NEFA was abrogated by AMPK inhibitor dorsomorphin. Furthermore, transfection with LKB1 siRNA (si-LKB1) largely abolished the activation effect of nuciferine on AMPK. Overall, nuciferine can protect bMECs from excessive NEFA-induced lipid accumulation, apoptosis, and impaired migration by activating LKB1/AMPK signaling pathway.