基于代谢组学的菊粉改善脂质代谢紊乱的机制研究
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摘要
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.
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.
引文
[1] 代燕丽,邹宇晓,刘凡,等.植物多酚干预脂质代谢紊乱作用机制研究进展[J].中国中药杂志,2015,40(21):4136- 4141.
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[7] 朱云云.麦冬多糖MDG- 1改善膳食诱导肥胖小鼠糖脂代谢紊乱的机制研究[D].上海:上海中医药大学,2014:13- 27.
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[9] 张娜,李晶,宋佳,等.低聚果糖靶向调节肠道菌群缓解力竭运动导致的脂质代谢紊乱[J].现代食品科技,2017,33(5):7- 13.
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[12] 赵春艳,阿基业,曹蓓,等.代谢组学在代谢性疾病研究中的进展[J].中国临床药理学与治疗学,2011,16(4):439- 446.
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[14] KIMURA I,OZAWA K,INOUE D,et al. The gut microbiota suppresses insulin- mediated fat accumulation via GPR43[J].Nat Commun,2013,4:1829.
[15] 王璐璇,刘玥宏,朱继开,等.短链脂肪酸在疾病治疗中的研究进展[J].世界华人消化杂志,2017,25(13):1179- 1186.
[16] DEN B G,BLEEKER A,GERDING A,et al. Short- Chain Fatty Acids Protect Against High- Fat Diet- Induced Obesity via a PPARγ- - Dependent Switch From Lipogenesis to Fat Oxidation[J].Diabetes,2015,64(7):2398- 2408.
[17] 吴水芸. 高脂肥胖对肠道微生态、短链脂肪酸的影响[D].镇江:江苏大学,2016
[18] YADAV H,LEE J H,LIOYD J,et al. Beneficial metabolic effects of a probiotic via butyrate- induced GLP- 1 hormone secretion[J].J Bio Chem,2013,288(35):25088- 25097.
[19] 辛衍代,季虹,刘兴艳,等.基于气相色谱- 质谱的肥胖抵抗大鼠尿液代谢组学研究[J].医学研究杂志,2012,41(12):95- 99.
[20] 范宝妍,朱海波.大黄素对高脂血症金黄地鼠脂代谢紊乱的改善作用[J].中国医药导报,2014,11(24):4- 8.
[21] ZHANG Q,WANG G J,A J Y,et al. Application of GC/MS- based metabonomic profiling in studying the lipid- regulating effects of Ginkgo biloba extract on diet- induced hyperlipidemia in rats[J].Acta Pharmacol Sin,2009,30(12):1674- 1687.
[22] 唐丹丽,佟琳,张华敏,等.痰瘀同治方对高脂血症心肌缺血再灌注损伤大鼠血脂及代谢组学影响的实验研究[J].中国中医基础医学杂志,2013,19(1):41- 43.
[23] 王旭方. 糖尿病肾病患者血清及尿液尿代谢组学特点及其临床意义[D].南京:南京大学,2012.
[24] 陶秀梅. “肾阳虚”模型及证候的代谢组学研究[D].上海:上海交通大学,2009.
[2] 周君一.脂质代谢紊乱患者的营养治疗[J].现代中西医结合杂志,2005,14(21):2833- 2834.
[3] 申利红,王建森,李雅,等.植物多糖的研究及应用进展[J].中国农学通报,2011,27(2):349- 352.
[4] 张泽生,刘亚萍,李雨蒙,等.菊粉的研究与开发[J].中国食品添加剂,2017 (10):183- 188.
[5] 彭英云,郑清,张涛.菊粉的功能与利用[J].食品研究与开发,2012,33(10):236- 240.
[6] 李雨露,刘丽萍,佟丽媛.菊粉的特性及在食品中的应用[J].食品工业科技,2013,34(13):392- 394.
[7] 朱云云.麦冬多糖MDG- 1改善膳食诱导肥胖小鼠糖脂代谢紊乱的机制研究[D].上海:上海中医药大学,2014:13- 27.
[8] 孙苏园,杨柏灿.中药调控脂质代谢作用机制的研究发展[J].医学综述,2015,21(8):1379- 1381.
[9] 张娜,李晶,宋佳,等.低聚果糖靶向调节肠道菌群缓解力竭运动导致的脂质代谢紊乱[J].现代食品科技,2017,33(5):7- 13.
[10] 朱立猛.菊粉对小鼠肠道微生物调节作用的研究[D].烟台:中国科学院烟台海岸带研究所,2017.
[11] 张璐,周林康,廖榕玉,等.高脂饮食中添加短链菊粉对小鼠肠道菌群的影响[J].现代生物医学进展,2017,17(22):4201- 4206.
[12] 赵春艳,阿基业,曹蓓,等.代谢组学在代谢性疾病研究中的进展[J].中国临床药理学与治疗学,2011,16(4):439- 446.
[13] BERNI CANANI R,DI COSTANZO M,LEONE L. The epigenetic effects of butyrate:potential therapeutic implications for clinical practice[J].Clin Epigenetics,2012,4(1):1- 7.
[14] KIMURA I,OZAWA K,INOUE D,et al. The gut microbiota suppresses insulin- mediated fat accumulation via GPR43[J].Nat Commun,2013,4:1829.
[15] 王璐璇,刘玥宏,朱继开,等.短链脂肪酸在疾病治疗中的研究进展[J].世界华人消化杂志,2017,25(13):1179- 1186.
[16] DEN B G,BLEEKER A,GERDING A,et al. Short- Chain Fatty Acids Protect Against High- Fat Diet- Induced Obesity via a PPARγ- - Dependent Switch From Lipogenesis to Fat Oxidation[J].Diabetes,2015,64(7):2398- 2408.
[17] 吴水芸. 高脂肥胖对肠道微生态、短链脂肪酸的影响[D].镇江:江苏大学,2016
[18] YADAV H,LEE J H,LIOYD J,et al. Beneficial metabolic effects of a probiotic via butyrate- induced GLP- 1 hormone secretion[J].J Bio Chem,2013,288(35):25088- 25097.
[19] 辛衍代,季虹,刘兴艳,等.基于气相色谱- 质谱的肥胖抵抗大鼠尿液代谢组学研究[J].医学研究杂志,2012,41(12):95- 99.
[20] 范宝妍,朱海波.大黄素对高脂血症金黄地鼠脂代谢紊乱的改善作用[J].中国医药导报,2014,11(24):4- 8.
[21] ZHANG Q,WANG G J,A J Y,et al. Application of GC/MS- based metabonomic profiling in studying the lipid- regulating effects of Ginkgo biloba extract on diet- induced hyperlipidemia in rats[J].Acta Pharmacol Sin,2009,30(12):1674- 1687.
[22] 唐丹丽,佟琳,张华敏,等.痰瘀同治方对高脂血症心肌缺血再灌注损伤大鼠血脂及代谢组学影响的实验研究[J].中国中医基础医学杂志,2013,19(1):41- 43.
[23] 王旭方. 糖尿病肾病患者血清及尿液尿代谢组学特点及其临床意义[D].南京:南京大学,2012.
[24] 陶秀梅. “肾阳虚”模型及证候的代谢组学研究[D].上海:上海交通大学,2009.
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