Nuciferine Ameliorates Nonesterified Fatty Acid-Induced Bovine Mammary Epithelial Cell Lipid Accumulation, Apoptosis, and Impaired Migration via Activating LKB1/AMPK Signaling Pathway
Jinxia Li, Chenchen Zhao, Menglin Liu, Linfang Chen, Yiwei Zhu, Wenwen Gao, Xiliang Du, Yuxiang Song, Xinwei Li, Guowen Liu, Lin Lei, Haihua Feng
Abstract
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.