Title

Regulation of hepatic cholesterol and lipoprotein metabolism by corn fiber oil and sitostanol in guinea pigs

Date of Completion

January 2001

Keywords

Health Sciences, Nutrition

Degree

Ph.D.

Abstract

Elevated levels of plasma cholesterol constitute a major risk factor for coronary heart disease (CHD). A dietary approach is the corner-stone for any lipid lowering regimen. However, non-traditional foods or nutraceuticals are emerging as dietary adjuncts to lower plasma cholesterol levels. ^ The purpose of these studies was to evaluate the cholesterol-lowering properties of corn fiber oil (CFO) in guinea pigs and to identify potential mechanisms involved in its hypocholesterolemic effect. Guinea pigs were chosen as the animal model because of their similarities to humans with respect to cholesterol and lipoprotein metabolism. ^ Male Hartley guinea pigs were fed diets containing increasing doses of CFO: 0 (control), 5, 10 or 15g/100 g diet. Total fat was adjusted to 15g/100 g in all diets with regular corn oil. Diets contained 0.25g/100g cholesterol. A positive control group (LC) with low dietary cholesterol (0.04 g/100 g) was also included. In additional experiments, guinea pigs were fed increasing doses of sitostanol (SI) (0.75, 1.5 and 2.25 g/100g SI) to determine if SI is the active ingredient in CFO. Plasma total and low-density lipoprotein (LDL) cholesterol concentrations were significantly lower with increasing doses of CFO and SI. Guinea pigs fed CFO and SI had lower hepatic cholesterol compared to controls. ^ The total fecal neutral sterol excretion was enhanced in the CFO and SI groups compared to the control, indicating a decrease in cholesterol absorption with CFO/SI intake. Cholesterol 7 α hydroxylase, the regulatory enzyme of bile acid synthesis was also up-regulated by CFO. CFO treatment also lowered the hepatic microsomal cholesterol pool, which was paralleled by an induction of hepatic LDL receptor mRNA. ^ These results suggest that SI is the active ingredient in CFO. CFO/SI exert their hypocholesterolemic effect by reducing cholesterol absorption and increasing bile acid output, which results in lower concentrations of cholesterol in liver. This reduction in hepatic cholesterol alters hepatic cholesterol homeostasis and affects the circulating lipoproteins. In addition, the reduction in the microsomal free cholesterol pool upregulates the hepatic LDL receptors leading to the observed decrease in plasma LDL cholesterol concentrations with CFO/SI intake. ^