Daily Dose of Bovine Lactoferrin Prevents Ethanol-Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota
Daily Dose of Bovine Lactoferrin Prevents Ethanol-Induced Liver Injury and Death in Male Mice by Regulating Hepatic Alcohol Metabolism and Modulating Gut Microbiota
复制标题
每日剂量的牛乳铁蛋白通过调节肝脏酒精代谢和调节肠道微生物群来预防雄性小鼠乙醇引起的肝损伤和死亡
DOI：
10.1002/mnfr.202100253
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发表时间：
2021-08-10
影响因子：
5.2
通讯作者：
Qin, Liqiang
中科院分区：
文献类型：
--
作者：
Li, Deming;He, Qian;Qin, Liqiang
范围乳铁蛋白(LF)对肝脏具有保护作用，但能否预防酒精性肝损伤(ALI)尚不清楚。方法和结果4组雄性C57BL/6J小鼠分别饲喂不同的饲料，即对照组(CON)和乙醇(EtoH)组，低剂量LF组(LLF)和高剂量LF组(HLF)分别用0.4%和4%酪蛋白替代AIN-93g饲料。ALI是通过随意给予20%乙醇并结合四个“暴饮暴食”而诱发的。LF能显著降低乙醇诱导的死亡率。LF促进乙醛脱氢酶-2(ALDH2)的表达，抑制细胞色素P450 2E1(CYP2E1)的过度表达，从而降低肝脏超氧化物歧化和炎症水平，最终达到减轻肝损伤的目的。然而，HLF会增加乙酰辅酶A羧基酶和脂肪酸合成酶的蛋白水平，这表明过量摄入可能会削弱LF的有益作用。此外，LLF还增加了阿克曼氏菌和乳杆菌的相对丰度。此外，研究表明，在正常情况下，LF可能以其消化产物的形式发挥作用，而不是完整的LF分子。结论LLF可改善ALI，其机制可能与调节肝脏酒精代谢和调节肠道微生物区系有关。然而，过量的LF摄入可能会导致益处减少。
Scope Lactoferrin (Lf) possess a protective potential to liver, but whether it can prevent alcoholic liver injury (ALI) remains unclear. Methods and Results Four groups of male C57BL/6J mice are fed with different diets, namely, AIN-93G diet for control (CON) and ethanol (EtOH) groups, and AIN-93G diet with 0.4% and 4% casein replaced by Lf for low-dose Lf (LLf) and high-dose Lf (HLf) groups, respectively. ALI is induced by giving 20% ethanol ad libitum combined with four "binges". Lf can remarkably decrease EtOH-induced mortality. Lf promotes aldehyde dehydrogenase-2 (ALDH2) expression and suppressing cytochrome P450 2E1 (CYP2E1) overexpression, resulting in the reduced hepatic superoxide and inflammation levels, which ultimately leads to the hepatic injury alleviation. However, HLf increases acetyl-CoA carboxylase and fatty acid synthase protein levels, which suggests that excessive intake may weaken the beneficial effects of Lf. Moreover, LLf increases the relative abundances of Akkermansia and Lactobacillus. Additionally, the study shows that Lf likely exerts action in its digestive product forms rather than intact Lf molecular in normal condition. Conclusion LLf can ameliorate ALI, which is associated with the regulation of hepatic alcohol metabolism and the modulation of gut microbiota. However, excessive Lf intake may result in a diminished benefit.