Effect of squalene supplementation on HMG CoA Reductase in rats fed high fat diet

Abstract

Squalene a 30-carbon hydrocarbon obtained from shark liver oil is an intermediate in the synthesis of all plant and animal sterols including steroid hormones, cholesterol, and vitamin D. Studies have revealed that intake of squalene rich foods affords a cardiovascular benefit and protects from vascular disease-related mortality. It is also known to lower plasma lipid fractions that may be responsible for this effect. In our study in albino rats, we aim to show molecular evidence of the effect of squalene on the proteins of lipid metabolism through proteomics approach. Five groups of rats designated as control/Group 1, fed diet with normal fat content; squalene-fed diet with normal fat content, Group 2; high fat diet-fed Group 3, high fat diet fed groups 4 and 5 supplemented with squalene at 0.025 and 0.05 per cent of body weight respectively were taken for the study. After the experimental feeding period of 27 days, rats were sacrificed and serum and liver tissue were taken for analysis. The effect of squalene on the mRNA expression of HMG CoA Reductase, the rate limiting enzyme in cholesterol biosynthesis has been studied. Western blotting approach was also used to determine the level of the enzyme HMG CoA Reductase in liver of rats of all experimental groups. Biochemical analysis of lipid fractions show that feeding of squalene resulted in lowering of total cholesterol and LDL cholesterol, triglycerides, but increased the levels of HDL cholesterol in squalene supplemented high fat diet fed rats in groups 4 and 5. No significant changes were observed in the content of phospholipids across the groups. mRNA expression of HMG CoA Reductase was significantly enhanced in Group 5, the high fat diet fed group that was supplemented with higher level of squalene when compared to Control group and Group 4 the high fat diet fed group that was supplemented with lower level of squalene. Fish oil feeding has resulted in lowering of serum total and LDL cholesterol and triglycerides. At the same time hepatic expression of HMG CoA Reductase was lowered which is important as this would mean lower rate of cholesterol synthesis.