基于脂质组学研究骆驼乳对小鼠非酒精性脂肪肝的缓解作用

The Alleviating Mechanism of Camel Milk on Non-alcoholic Fatty Liver Disease in Mice Based on Lipidomics

目的:探讨骆驼乳对小鼠非酒精性脂肪肝(NAFLD)的缓解作用。方法:将30只C57BL/6J小鼠随机分配为3组:对照组(NC组)、模型组(Mod组)和骆驼乳组(CaM组)。对照组饲喂对照饲料,模型组和骆驼乳组饲喂高脂饲料,每日给骆驼乳组灌胃骆驼乳。试验持续12周,建立NAFLD模型。通过对生化指标、肝脏病理结构和肝脏脂质组的分析,明确骆驼乳缓解小鼠NAFLD的作用机制。结果:在骆驼乳的干预下,NAFLD小鼠的体质量、血糖和肝脏指数显著降低,分别为31.45g、8.85 mmol/mL、3.98%(P<0.05);血清总甘油三酯(TG)、总胆固醇(TC)和低密度脂蛋白(LDL-c)水平显著降低,分别为0.657 mmol/mL、4.689 mmol/mL、9.923μmol/mL(P<0.05);肝脏TG和TC水平显著降低,分别为0.034,0.009 mmol/mL(P<0.05);肝脏组织结构完整清晰,肝脏中脂质积累减少。脂质组学分析结果表明,CaM组小鼠肝脏中的胆碱(CEs)、甘油二酯(DG)、不饱和甘油三酯(TGs)、磷脂酰胆碱(PC)和溶血磷脂酰胆碱(LPCs)的相对水平增加;脂质代谢物富集于鞘脂类代谢、甘油酯类代谢和甘油磷脂类代谢。结论:骆驼乳通过调控NAFLD小鼠鞘脂类代谢、甘油酯类代谢和甘油磷脂类代谢改变小鼠肝脏脂质谱,缓解NAFLD。

Objective:To investigate the alleviating mechanism of camel milk on non-alcoholic fatty liver disease(NAFLD)in mice.Methods:Thirty C57BL/6J mice were randomly assigned into three groups:negative control group(NC group),model group(Mod group)and camel milk group(CaM group).The negative control group was fed control diets,the model and camel milk groups were fed high-fat diets,and camel milk was given daily by gavage to the camel milk group mice.The experiment lasted for 12 weeks,and the NAFLD model was established.The alleviation mechanism of NAFLD in mice by camel milk was investigated by analyzing biochemical indices,liver pathological structure and liver lipidome.Results:With the intervention of camel milk,the body weight,blood glucose and liver index of NAFLD mice were significantly reduced to 31.45 g,8.85 mmol/mL and 3.98%,respectively(P<0.05);the levels of total triglyceride(TG),total cholesterol(TC)and low density lipoprotein(LDL-c)in serum were significantly reduced to 0.657 mmol/mL,4.689 mmol/mL,and 9.923μmol/mL,respectively(P<0.05);the levels of TG and TC in liver were dramatically reduced to 0.034 mmol/mL and 0.009 mmol/mL,respectively(P<0.05);liver tissue structure was intact and clear,and the lipid accumulation was reduced in the liver.Lipidomic analysis showed that the relative levels of choline(CEs),diglycerides(DGs),unsaturated triglycerides(TGs),phosphatidylcholine(PC)and lysophosphatidylcholine(LPCs)were increased in the liver of mice in the CaM group;lipid metabolites were enriched in sphingolipid metabolism,glycerol ester metabolism and glycerophospholipid metabolism.Conclusion:Camel milk alleviates NAFLD by modulating sphingolipid metabolism,triglyceride metabolism and glycerophospholipid metabolism in mice with NAFLD by altering liver lipid profiles.