Background – Squalene is a component of shark liver oil and has been speculated to have cholesterol reducing properties. High levels of total and LDL cholesterol have been shown to contribute to the development of chronic heart disease. The liver is central to the regulation of cholesterol metabolism and dietary intervention has long been recognized as a primary means to reduce the risks of chronic heart disease and related ailments.
Objectives – To determine the effect of dietary squalene supplementation on gene transcripts associated with liver cholesterol metabolism. Specifically the effect of squalene supplementation on mRNA levels for proteins that regulate cholesterol biosynthesis (HMDH & ERG1), cholesterol elimination (SRB1), bile synthesis (CP7A1 & CP27A) and cholesterol excretion by the liver into bile (ABCG5 & ABCG8) was investigated.
Design – Rats (n=32) were divided into four groups and supplemented for 12 weeks. Groups one and two were fed a cholesterol rich diet for six weeks followed by six weeks of a cholesterol rich diet plus 1.75mg/day of squalene or 3.5 mg/day. Group three was fed a cholesterol rich diet for 12 weeks and group four was fed standard rat chow for 12 weeks. Blood lipid levels were monitored during the study and liver gene expression was determined at the conclusion of the feeding trial via RT-PCR.
Outcomes – 3.5 mg/day of squalene lowered total and LDL cholesterol in rats consuming a cholesterol rich diet. This dose of squalene also resulted in constant levels of HMDH and ERG1 whereas the cholesterol rich diet halved mRNA levels of these enzymes. Furthermore 3.5 mg/day of squalene caused a greater than 3.0 fold increase in mRNA levels of the proteins SRB1, CP7A1, CP27A and ABCG5.
Conclusion – Dietary squalene supplementation at a dose of 3.5 mg/day lowers total and LDL cholesterol in rats consuming a cholesterol rich diet. These reductions in cholesterol levels may be due to increased cholesterol elimination, bile synthesis and cholesterol excretion by the liver into bile mediated by changes in gene expression of key enzymes involved in these metabolic pathways