Flavonoids in the Amelioration of Hypertiglyceridemia

描述（由申请人提供）：本研究项目的长期目标是检查补充和替代医学（CAM）富含类生物素的提取物（即绿色茶叶提取物、柑橘类生物素和芦丁）对高胆固醇血症模型中肝富含类生物素脂蛋白产生的调节的影响。富含类黄酮的提取物被认为可以预防心血管疾病（CVD），这在很大程度上是通过其对低密度脂蛋白（LDL）氧化的抑制作用。这些化合物在治疗高脂血症中的潜在益处最近也已在动物和人类研究中显示。然而，这种降脂作用的分子机制尚未完全了解。我们最近已经表明，柑橘双黄酮给药高脂血症-胰岛素抵抗（HIR）仓鼠降低血液甘油三酯水平，通过抑制肝微粒体甘油三酯转移蛋白（MTP）蛋白表达和二酰基甘油酰基转移酶（DGAT）活性。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。其他脂肪生成酶在极低密度脂蛋白生成中的作用有待研究。此外，肝脏apoB 100-VLDL的组装和分泌是否改变需要解决。此外，尚不清楚是否所有的生物素都具有降低胆固醇的能力。因此，本研究使用血浆和分离肝细胞的具体目的是研究富含类生物素的提取物对HIR仓鼠体内和体外VLDL产生的影响。这将通过测量血浆中VLDL分泌的速率，并通过使用分离的肝细胞、apoB-100和甘油三酯的合成和分泌以及脂肪生成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.