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.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AT001286-02
Application #
6787622
Study Section
Special Emphasis Panel (ZAT1-DB (07))
Program Officer
Moen, Laura K
Project Start
2003-08-01
Project End
2007-04-30
Budget Start
2004-05-01
Budget End
2007-04-30
Support Year
2
Fiscal Year
2004
Total Cost
$170,375
Indirect Cost
Name
University of Hawaii
Department
Type
Schools of Medicine
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822
Maiyoh, Geoffrey K; Kuh, Joan E; Casaschi, Adele et al. (2007) Cruciferous indole-3-carbinol inhibits apolipoprotein B secretion in HepG2 cells. J Nutr 137:2185-9
Li, Rachel W; Douglas, Teresa D; Maiyoh, Geoffrey K et al. (2006) Green tea leaf extract improves lipid and glucose homeostasis in a fructose-fed insulin-resistant hamster model. J Ethnopharmacol 104:24-31
Li, Rachel W; Theriault, Andre G; Au, Karen et al. (2006) Citrus polymethoxylated flavones improve lipid and glucose homeostasis and modulate adipocytokines in fructose-induced insulin resistant hamsters. Life Sci 79:365-73