Nuciferine Ameliorates\nNonesterified Fatty Acid-Induced\nBovine Mammary Epithelial Cell Lipid Accumulation, Apoptosis, and\nImpaired Migration via Activating LKB1/AMPK Signaling Pathway

Abstract

High blood concentrations of nonesterified fatty acids\n(NEFAs)\nprovoke various metabolic disorders and are associated with mammary\ntissue injury and decreased milk production in dairy cows. Nuciferine,\nan alkaloid found in Nelumbo nucifera leaves, has great potential for correcting lipid metabolism derangements\nand lipotoxicity. In this study, we evaluated the lipotoxicity induced\nby excessive NEFA in bovine mammary epithelial cells (bMECs) and investigated\nwhether nuciferine alleviates NEFA-induced lipotoxicity and the underlying\nmolecular mechanisms. We found that excessive NEFA (1.2 and 2.4 mM)\ninduced lipid accumulation, apoptosis, and migration ability impairment\nin bMECs, whereas nuciferine could ameliorate these disarrangements,\nas indicated by decreasing triglyceride content, protein abundance\nof SREBP-1c, cytoplasmic cytochrome <i>c</i>, and cleaved\ncaspase-3 and increasing protein abundance of PPARα and migration\nability. Moreover, nuciferine could reverse NEFA-induced LKB1/AMPK\nsignaling inhibition, and the protective effect of nuciferine on lipotoxicity\ncaused by NEFA was abrogated by AMPK inhibitor dorsomorphin. Furthermore,\ntransfection with LKB1 siRNA (si-LKB1) largely abolished the activation\neffect of nuciferine on AMPK. Overall, nuciferine can protect bMECs\nfrom excessive NEFA-induced lipid accumulation, apoptosis, and impaired\nmigration by activating LKB1/AMPK signaling pathway.