Although the incidence of coronary heart disease (CHD) is lower in premenopausal women than in men of the same age, the risk of CHD is increased substantially after menopause including elevated levels of serum lipids. Evidence indicates that green tea or its catechins lower the blood levels of cholesterol and retard the development or progression of atherosclerosis in animal models. At present, how green tea or its bioactive components (catechins) influence cholesterol metabolism is unknown. Furthermore, little information exists on whether green tea can effectively prevent the postmenopausal increases in blood cholesterol and other lipids. This study proposes the following specific aims using ovariectomized middle-aged rats as a model: 1) to evaluate the efficacy of green tea extract (GTE) and catechins in inhibiting the intestinal absorption of cholesterol; 2) to determine whether GTE inhibits the hepatic synthesis and release of cholesterol into the blood circulation; and 3) to examine whether GTE alters the biliary secretion of cholesterol and bile acids. Fischer-344 female rats (12-14 months old) will be ovariectomized to mimic the age and postmenopausal state (loss of ovarian function) of women. To measure the intestinal absorption of cholesterol and other lipids, the superior mesenteric lymph duct will be cannulated. The amounts of 14C-cholesterol released into the lymph will be monitored during intraduodenal infusion of a lipid emulsion containing 14C-labeled cholesterol in the presence or absence of GTE or its specific catechins. Using 3H-labeled water as the tracer of cholesterol biosynthesis, we will determine the rate and amount of 3H-labeled cholesterol released from the liver into the blood circulation in rats fed GTE or its catechins in drinking water. Rats with bile and lymph duct cannula will be used to study the effect of GTE on the rates and amounts of cholesterol and bile acids excreted via the biliary route during fasting and in response to lipid infusion. The proposed study will provide new insight into how GTE or catechins influence cholesterol homeostasis and blood cholesterol levels. This study also will yield valuable information on whether green tea and catechins can be recommended as a means of lowering cholesterol absorption, and will form the basis for further mechanistic or clinical investigations. ? ?
