Flavonoids in the Amelioration of Hypertiglyceridemia

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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.