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首页> 外文学位 >The effect of proalgazyme and its subfractions on lipid metabolism in diet induced hypercholesterolemic hamsters: Correlation with plasma metabolomic profile.
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The effect of proalgazyme and its subfractions on lipid metabolism in diet induced hypercholesterolemic hamsters: Correlation with plasma metabolomic profile.

机译：饮食诱发的高胆固醇血症仓鼠中原酶及其亚组分对脂质代谢的影响：与血浆代谢组学特征的相关性。

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摘要

Background: Plasma HDL cholesterol levels are inversely related to cardiovascular disease, which is the leading cause of death worldwide. This study investigated the preventative effect of an algae infusion, ProAlgaZyme (PAZ) and its subfractions (F1, F2, F3, F4) on plasma HDL in a hamster model. Further, the study aimed to identify the biologically active fraction of PAZ and to determine the therapeutic efficacy of the fraction in diet induced hypercholesterolemic hamsters over time. Also, the current study investigated the changes in plasma metabolomic profile produced due to the interventions, and correlated the results with the lipoprotein profile of the hamsters.;Methods: Eighty male golden Syrian hamsters (8 weeks old) were randomized into controls (CW and CP) or high fat diet (HW, HP, HF1, HF2, HF3, and HF4). Further, the study aimed to determine the therapeutic effect of the active fraction of PAZ. For this, 40 male Golden Syrian hamsters were fed a high fat diet for 4 weeks prior to randomization into 5 groups, based on the number of days they received the treatment.;Results: Non-HDL cholesterol was significantly reduced in the HP (P < 0.05), HF3 and HF4 (P < 0.001) groups as compared with the HW group, while HDL cholesterol showed a significant increase in the HP, HF3, and HF4 groups (P < 0.001). Moreover, the total cholesterol/HDL ratio was significantly improved in the HP, HF1, and HF2 (P < 0.05), and HF3 and HF4 (P < 0.001) groups. Real-time quantitative polymerase chain reaction showed a significant increase in hepatic ApoA1 (HP, HF4) and ABCA1 (HF3, HF4) expression, consistent with an increase in HDL production, biogenesis, and maturation. A two-fold increase in SRB1 expression indicates that HF4 further augments the reverse cholesterol transport mechanism. Reduction of CETP expression (HF4) is consistent with a decrease in the transfer of cholesteryl ester to LDL, further increasing the amount of cholesterol held as HDL particles. NMR metabolomics approach showed a significant decrease in the concentration of several small molecular weight molecules, including branched chain amino acids and phosphocholine-containing molecules, in groups HP and HF4, when compared with HW group. Since, F4 exhibited the most influence on plasma lipid and metabolomic profile, it was further tested for its therapeutic effect.;Plasma HDL was significantly increased in T3 (P < 0.05) and T21 (P < 0.001), while non-HDL cholesterol was significantly reduced in T3, T7, T10 (P < 0.001) and T14, T21 (P < 0.01). Moreover, the total cholesterol/HDL was significantly lower in all groups (P < 0.001) as compared with T0. Quantitative RT-PCR showed an increase in Apo A1 expression in T10 (3x) and T21 (6x) groups. NMR data followed by multivariate analysis showed a clear separation between T0 and T21 groups, indicating a difference in their metabolomic profiles. Plasma concentrations of choline, phosphocholine, glycerol-phosphocholine, betaine and carnitine metabolites were significantly lowered in T21 group. These metabolites are associated with a reduced risk for atherosclerosis and cardiovascular disease.;Conclusion: ProAlgaZyme and its subfractions significantly improved the plasma cholesterol profile by lowering non-HDL and increasing HDL, possibly via the reverse cholesterol transport mechanism. Also, the concentration of several pro-atherogenic small molecular weight metabolites has been decreased, indicating that PAZ and F4 can be used as a preventative agent for hypercholesterolemia and atherosclerosis. Moreover, treatment with F4 also significantly improved plasma lipid profile by increasing HDL and lowering non-HDL cholesterol, and reducing key risk factor metabolites for atherosclerosis and cardiovascular disease. (Abstract shortened by UMI.).
机译：背景：血浆高密度脂蛋白胆固醇水平与心血管疾病成反比，心血管疾病是全球死亡的主要原因。这项研究调查了藻类注射液ProAlgaZyme（PAZ）及其子级分（F1，F2，F3，F4）对仓鼠模型中血浆HDL的预防作用。此外，该研究旨在鉴定PAZ的生物活性部分，并确定该部分在饮食诱导的高胆固醇仓鼠中的治疗效果。此外，本研究还研究了干预措施引起的血浆代谢组学谱的变化，并将结果与​​仓鼠的脂蛋白谱相关联。;方法：将80只雄性叙利亚金黄仓鼠（8周龄）随机分为对照组（CW和CP）或高脂饮食（HW，HP，HF1，HF2，HF3和HF4）。此外，该研究旨在确定PAZ活性成分的治疗效果。为此，根据接受治疗的天数，将40只雄性金叙利亚仓鼠随机分为5组，然后喂4周高脂饮食;结果：HP中非HDL胆固醇显着降低（P <0.05），HF3和HF4组（P <0.001）与HW组相比，而HDL胆固醇在HP，HF3和HF4组中显着增加（P <0.001）。此外，HP，HF1和HF2（P <0.05）以及HF3和HF4（P <0.001）组的总胆固醇/ HDL比得到显着改善。实时定量聚合酶链反应显示肝ApoA1（HP，HF4）和ABCA1（HF3，HF4）表达显着增加，与HDL产生，生物发生和成熟的增加一致。 SRB1表达增加两倍，表明HF4进一步增强了胆固醇的逆向转运机制。 CETP表达（HF4）的减少与胆固醇酯向LDL转移的减少一致，这进一步增加了HDL颗粒中胆固醇的含量。 NMR代谢组学方法显示，与HW组相比，HP和HF4组中几个小分子量分子（包括支链氨基酸和含磷胆碱的分子）的浓度显着降低。由于F4对血浆脂质和代谢组学的影响最大，因此对其治疗效果进行了进一步测试。;血浆HDL在T3和T21中显着增加（P <0.05）和T21（P <0.001），而非HDL胆固醇则显着增加。 T3，T7，T10（P <0.001）和T14，T21（P <0.01）显着降低。此外，与T0相比，所有组的总胆固醇/ HDL均显着降低（P <0.001）。定量RT-PCR显示在T10（3x）和T21（6x）组中Apo A1表达增加。 NMR数据和随后的多元分析表明，T0和T21组之间存在明显的分离，表明它们的代谢组学谱存在差异。 T21组的胆碱，磷酸胆碱，甘油-磷酸胆碱，甜菜碱和肉碱代谢产物的血浆浓度显着降低。这些代谢产物与降低动脉粥样硬化和心血管疾病的风险有关。结论：ProAlgaZyme及其亚组分可通过降低非HDL和增加HDL显着改善血浆胆固醇水平，可能是通过逆向胆固醇转运机制。同样，几种促动脉粥样硬化的小分子量代谢物的浓度也降低了，表明PAZ和F4可用作高胆固醇血症和动脉粥样硬化的预防剂。此外，用F4进行治疗还可以通过增加HDL和降低非HDL胆固醇，减少动脉粥样硬化和心血管疾病的关键危险因素代谢物来显着改善血浆脂质状况。 （摘要由UMI缩短。）。

著录项

  • 作者

    Geamanu, Andreea.;

  • 作者单位

    Wayne State University.;

  • 授予单位 Wayne State University.;
  • 学科 Health Sciences Nutrition.;Health Sciences Alternative Medicine.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 156 p.
  • 总页数 156
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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