Title

Gender and hormonal status modulate the hypolipidemic mechanisms of dietary soluble fiber in the guinea pig

Date of Completion

January 2001

Keywords

Agriculture, Animal Culture and Nutrition|Health Sciences, Nutrition

Degree

Ph.D.

Abstract

Coronary heart disease (CHD) is the single leading cause of death in the United States. Elevated plasma cholesterol levels and gender constitute two of the major risk factors for CHD. Dietary soluble fiber (SF) has consistently been shown to reduce plasma LDL cholesterol concentrations. ^ The purpose of these studies was to assess distinctive effects of gender and hormonal status on secondary mechanisms by which dietary SF lowers plasma LDL cholesterol. Guinea pigs were used as the animal model because their lipoprotein profile and response to dietary fiber are similar to humans. ^ Male, female and ovariectomized (to mimic menopause) guinea pigs were allocated to two dietary treatments differing only in fiber source: control diet contained 10% cellulose and 2.5% guar gum while SF diet contained 5% psyllium, 5% pectin and 2.5% guar gum. SF intake significantly reduced plasma total and LDL cholesterol, triacylglycerol (TAG) and apo B concentrations. ^ However, ovariectomized guinea pigs, in both diet groups, had highest plasma LDL cholesterol, apo B and TAG concentrations. SF treatment yielded smaller cholesteryl ester-depleted LDL. Susceptibility of LDL to oxidation was reduced in males and females following SF intake but remained unaffected in ovariectomized guinea pigs. Female guinea pigs had higher plasma HDL and LDL α-tocopherol concentrations, compared to males. ^ Dietary SF altered hepatic cholesterol metabolism by effectively reducing hepatic free cholesterol, TAG and microsomal free cholesterol concentrations, while activities of HMG-CoA reductase and cholesterol 7α-hydroxylase (CYP7) were upregulated. Guinea pig CYP7 cDNA was cloned and partially sequenced for the first time. The nucleotide sequence showed 86% homology to the human CYP7 cDNA. Hepatic CYP7 mRNA abundance paralleled the increase in enzyme activity in guinea pigs fed the SF diet. Ovariectomized guinea pigs had the lowest activity and expression of hepatic CYP7 even after intervention with SF. ^ From these studies we conclude that induction of hepatic CYP7 activity and mRNA abundance by dietary SF intake is one of the major secondary mechanisms that may account, in large part, for the hypocholesterolemic effect of soluble fiber. Gender and hormonal status influence metabolic responses to dietary SF with estrogen deprivation leading to the most detrimental lipid profile for CHD risk. ^