基于代谢组学的菊粉改善脂质代谢紊乱的机制研究

Mechanism research on inulin improving lipid metabolism disorders based on metabolomics

目的:采用代谢组学技术研究菊粉对高脂饮食诱导的肥胖(DIO)小鼠脂质代谢紊乱的影响及其作用机制。方法:雄性C57BL/6J小鼠随机分为对照组、模型组和菊粉组,每组8只。对照组小鼠喂予普通饲料,模型组和菊粉组小鼠喂予高脂饲料诱导肥胖模型。造模8周后,菊粉组小鼠给予含8%菊粉的高脂饲料进行干预,对照组和模型组小鼠仍分别给予原饲料,继续喂养8周。试验期间每周记录小鼠体质量,末次给药后收集各组小鼠血清和粪便样本。全自动生化分析仪检测血清TC、TG、HDL-C和LDL-C的含量;气相色谱-飞行时间质谱(GC-TOF/MS)联用技术检测粪便样本,构建代谢轮廓谱,主成分分析(偏最小二乘法)比较组间代谢谱差异,筛选并鉴定差异性代谢物,分析代谢通路。结果:①菊粉干预第2周起,菊粉组小鼠体质量增长较模型组明显减缓;干预第6周,菊粉组小鼠平均体质量较模型组显著降低(P<0.05),并持续至第8周。②干预8周后,与模型组相比,菊粉组小鼠血清TC、TG、HDL-C和LDL-C含量均显著下降(P<0.05,P<0.01)。③代谢组学主成分分析显示组间代谢谱差异明显。共鉴定11种潜在的差异性代谢物,与模型组相比,菊粉干预可升高果糖、麦芽糖、次黄嘌呤、油酸、肌酸和丁酸的含量,并降低棕榈酸、丙酮酸、色氨酸、尿嘧啶、3-羟基丁酸的含量,且通路分析显示丁酸代谢、淀粉和蔗糖代谢、不饱和脂肪酸的生物合成、脂肪酸生物合成等途径与菊粉改善DIO小鼠脂质代谢紊乱密切相关。结论:菊粉可有效改善高脂饮食诱导的肥胖小鼠脂质代谢紊乱,其机制可能与丁酸代谢、淀粉和蔗糖代谢、脂肪酸合成等通路有关。

Objective: To study the effects and mechanisms of inulin on lipid metabolism disorders in high-fat diet induced obese(DIO) mice by metabolomics. Methods: Male C57 BL/6 J mice were randomly divided into the control group,model group and inulin group,8 mice in each group. The mice in the control group were fed with the normal diet,while the mice in the model group and inulin group were fed with the high-fat diet to induce obesity model. After modeling for 8 weeks,the mice in the inulin group were treated with the high-fat diet containing 8% inulin,while the other two groups were treated with their original diets,with a course of 8 weeks. The body mass of mice was recorded weekly during the trial. After the last administration,the serum and stool samples from each group were collected. The serum levels of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C) and low-density lipoprotein cholesterol(LDL-C) were determined by automatic biochemical analyzer. The fecal samples were detected by gas chromatography-time of flight mass spectrometry(GC-TOF/MS). The metabolic profiles were established,and the principal component analysis(partial least squares) was used to compare the differences in metabolic profiles between groups. The differential metabolites were screened and identified,and the metabolic pathways were analyzed. Results:①From the second week of inulin intervention,the body weight growth of mice in the inulin group was significantly slower than that in the model group. At the sixth week of inulin intervention,the average body weight of mice in the inulin group was significantly lower than that in the model group( P<0.05),which continued until the eighth week.(2)After intervention for 8 weeks,compared with the model group,the serum levels of TC,TG,HDL-C and LDL-C in the inulin group were significantly decreased( P<0.05,P<0.01).(3) Metabolomics principal component analysis showed significant differences in metabolic profiles among the three groups. A total of 11 potential differential metabolites were identified. Compared with the model group,inulin intervention could increase the contents of fructose,maltose,hypoxanthine,oleic acid,creatine and butyric acid,and reduce the contents of palmitic acid,pyruvate,tryptophan,uracil,3-hydroxybutyrate acid. Pathway analysis showed that butyric acid metabolism,starch and sucrose metabolism,biosynthesis of unsaturated fatty acids,fatty acid biosynthesis were closely related to the improvement of inulin on lipid metabolism disorder in DIO mice. Conclusion: Inulin can effectively improve the lipid metabolism disorder in obese mice induced by high-fat diet,and its mechanism may be related to the pathways such as butyric acid metabolism,starch and sucrose metabolism and fatty acid synthesis.