Understanding molecular mechanisms involved in the cholesterol -reducing action of dietary psyllium in rats
Abstract
The purpose of the present study was to identify specific molecular mechanisms involved in the hypocholesterolemic action of psyllium hydrocolloid via modification of bile acid synthesis and regulation of the enterohepatic circulation of bile acids. Psyllium, a source of dietary fiber rich in soluble components, results in lower serum cholesterol concentration in several species. Suggested mechanisms for the hypocholesterolemic effect include a greater excretion of fecal bile acids and up regulation of bile acid biosynthesis due to changes in the bile acid pool spectrum. In the first experiment, feeding psyllium to rats resulted in greater fecal bile acid and total steroid excretion as well as greater cholesterol 7α-hydroxylase (CYP7A) activity and mRNA levels compared to rats fed cellulose. This suggested that regulation of CYP7A mRNA expression levels are involved in the hypocholesterolemic action of dietary psyllium. Because more hydrophilic bile acids are less able to feedback inhibit CYP7A mRNA levels, it was proposed that changing the bile acid pool composition may be involved. Results of the second experiment confirmed results of the first experiment in a dose response fashion and also demonstrated that feeding psyllium resulted in greater ileal apical sodium dependent bile acid transporter (ASBT) mRNA levels; a putative mechanism for making the bile acid pool more hydrophilic. Finally, results of the third experiment using rat hepatocyte primary monolayer cultures, demonstrated that the small but significant changes in the bile acid spectrum of rats fed psyllium compared to rats fed cellulose (previously observed in our laboratory) directly regulates CYP7A mRNA expression levels. Taken together, results of these experiments suggest that the hypocholesterolemic action of dietary psyllium in rats involves multiple mechanisms including regulation of bile acid synthesis and the enterohepatic circulation of bile acids.
Degree
Ph.D.
Advisors
Story, Purdue University.
Subject Area
Nutrition|Anatomy & physiology|Animals
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