Flavonoids in the Amelioration of Hypertiglyceridemia

描述(申请人提供)：这项研究项目的长期目标是研究补充和替代医学(CAM)富含生物类黄酮的提取物(即绿茶叶提取物、柑橘类生物类黄酮和芦丁)对高甘油三酯血症模型中肝脏富含甘油三酯的脂蛋白生成的调节作用。富含生物黄酮类的提取物被认为可以预防心血管疾病，这在很大程度上是通过抑制低密度脂蛋白(LDL)氧化来实现的。这些化合物在治疗高脂血症方面的潜在益处最近也在动物和人类研究中得到了证明。然而，这种降脂作用的分子机制还不完全清楚。我们最近发现，给高甘油三酯血症-胰岛素抵抗(HIR)仓鼠服用柑橘生物类黄酮可通过抑制肝微粒体甘油三酯转移蛋白(MTP)蛋白表达和二酰甘油酰基转移酶(DGAT)活性来降低血甘油三酯水平。这些结果是初步的，需要在更大范围内得到证实。尽管如此，这些结果确实揭示了一个潜在的令人兴奋的研究领域。其他造脂酶在极低密度脂蛋白产生中的作用还有待探索。此外，肝脏载脂蛋白B100-极低密度脂蛋白的组装和分泌是否发生改变也需要解决。此外，目前还不知道是否所有的生物类黄酮都具有降低甘油三酯的能力。因此，本研究采用血浆和分离的肝细胞，研究富含生物黄酮类的提取物对HIR金黄地鼠体内和体外极低密度脂蛋白产生的影响。这将通过测量血浆中极低密度脂蛋白的分泌率，以及通过分离的肝细胞，载脂蛋白B-100和甘油三酯的合成和分泌，以及造脂酶的表达和活性来完成。通过了解这些产品的降脂功能，旨在为这些常用的CAM产品提供新的信息。

DESCRIPTION (provided by applicant): The long term goal of this research project is to examine the influence of complementary and alternative medicine (CAM) bioflavonoid-rich extracts (i.e. green tea leaf extracts, citrus bioflavonoids, and rutin) on the regulation of hepatic triglyceride-rich lipoprotein production in a hypertriglyceridemic model. Bioflavonoid-rich extracts have been claimed to protect against cardiovascular disease (CVD), in large part through its inhibitory effect on low density lipoprotein (LDL) oxidation. The potential benefit of these compounds in treating hyperlipidemia has also recently been shown in both animal and human studies. However, the molecular mechanisms for this lipid-lowering action are not fully understood. We have recently shown that a citrus bioflavonoid administered to hypertriglyceridemic-insulin resistant (HIR) hamsters lowered blood triglyceride levels through the inhibition of hepatic microsomal triglyceride transfer protein (MTP) protein expression and diacylglycerol acyltransferase (DGAT) activity. These results are preliminary and need to be confirmed on a larger scale. Nonetheless, these results do unveil a potentially exciting area of research. The role of other lipogenic enzymes in VLDL production needs to be explored. Also, whether or not the assembly and secretion of hepatic apoB100-VLDL is altered need to be addressed. Moreover, it is not known if all bioflavonoids possess a triglyceride-lowering ability. Therefore, the specific aim of this study using both plasma and isolated hepatocytes is to investigate the effect of bioflavonoid-rich extracts on the in vivo and ex vivo VLDL production in HIR hamsters. This will be done by measuring the rate in VLDL secretion in plasma, and by using isolated hepatocytes, the synthesis and secretion of apoB-100 and triglyceride, and lipogenic enzyme expression and activity. By understanding the lipid lowering function of these products, we aimed at providing new information of these commonly used CAM products.