Abstract：
Ketosis in dairy cows is often accompanied by the dysregulation of lipid homeostasis in the liver. Acetyl-coenzyme A acetyltransferase 2 (ACAT2) is specifically expressed in the liver and is important for regulating lipid homeostasis in ketotic cows. Lentinan (LNT) has a wide range of pharmacological activities, and this study investigates the protective effects of LNT on β-hydroxybutyrate (BHBA)-induced lipid metabolism disorder in bovine hepatocytes (BHECs) and elucidates the underlying mechanisms. BHECs were first pretreated with LNT to investigate the effect of LNT on BHBA-induced lipid metabolism disorder in BHECs. ACAT2 was then silenced or overexpressed to investigate whether this mediated the protective action of LNT against BHBA-induced lipid metabolism disorder in BHECs. Finally, BHECs were treated with LNT after silencing ACAT2 to investigate the interaction between LNT and ACAT2. LNT pretreatment effectively enhanced the synthesis and absorption of cholesterol, inhibited the synthesis of triglycerides, increased the expression of ACAT2, and elevated the contents of very low-density lipoprotein and low-density lipoprotein cholesterol, thereby ameliorating BHBA-induced lipid metabolism disorder in BHECs. The overexpression of ACAT2 achieved a comparable effect to LNT pretreatment, whereas the silencing of ACAT2 aggravated the effect of BHBA on inducing disorder in lipid metabolism in BHECs. Moreover, the protective effect of LNT against lipid metabolism disorder in BHBA-induced BHECs was abrogated upon silencing of ACAT2. Thus, LNT, as a natural protective agent, can enhance the regulatory capacity of BHECs in maintaining lipid homeostasis by upregulating ACAT2 expression, thereby ameliorating the BHBA-induced lipid metabolism disorder.
摘要：
奶牛的酮病通常伴随着肝脏中脂质稳态的失调。乙酰辅酶A乙酰转移酶2（ACAT2）在肝脏中特异性表达，对于调节酮症奶牛的脂质稳态很重要。香菇多糖(LNT)具有广泛的药理活性,本研究探讨了LNT对β-羟基丁酸酯（BHBA）诱导的牛肝细胞（BHECs）脂质代谢紊乱的保护作用，并阐明了其潜在机制。首先用LNT预处理BHECs以研究LNT对BHBA诱导的BHECs脂质代谢紊乱的影响。然后沉默或过表达ACAT2以研究这是否介导LNT对BHBA诱导的BHECs脂质代谢紊乱的保护作用。最后,沉默ACAT2后用LNT处理BHECs以研究LNT和ACAT2之间的相互作用。LNT预处理有效增强了胆固醇的合成和吸收，抑制甘油三酯的合成，ACAT2的表达增加，极低密度脂蛋白和低密度脂蛋白胆固醇的含量升高，从而改善BHBA诱导的BHECs脂质代谢紊乱。ACAT2的过表达达到了与LNT预处理相当的效果，而ACAT2的沉默加重了BHBA诱导BHECs脂质代谢紊乱的作用。此外，在BHBA诱导的BHECs中LNT对脂质代谢紊乱的保护作用在ACAT2沉默后被取消。因此，LNT,作为天然保护剂,可以通过上调ACAT2表达来增强BHECs维持脂质稳态的调节能力，从而改善BHBA诱导的脂质代谢紊乱。
