Title

Effects of dietary cholesterol and carbohydrate restriction on plasma and hepatic lipid metabolism, atherosclerosis and inflammation in guinea pigs

Date of Completion

January 2007

Keywords

Health Sciences, Nutrition

Degree

Ph.D.

Abstract

The main objective of this project was to evaluate the effects of dietary cholesterol and carbohydrate restriction on plasma and hepatic lipid metabolism, atherosclerosis and inflammation. The project was divided in 4 studies: in Study 1 and 2 Hartley male growing guinea pigs (GP) (10/group) were fed either a diet high in carbohydrate and low in cholesterol (Control) and two diets high in cholesterol: either high or low in carbohydrate (HChol and CR, respectively). In these two studies, plasma lipids, lipoprotein subfractions, hepatic cholesterol, ACAT activity and LDL-r and HMG-CoA reductase mRNA abundance were determined. For study 3 and 4, male adult GP (10/group) were fed with 2 diets with low cholesterol (one high and the other low in carbohydrate) and 2 with high cholesterol (one low and one high in carbohydrate). In study 3 the same parameters considered in the studies 1 and 2 were measured. For study 4 aortic lipid accumulation, inflammatory cytokines, sPLA2 activity and biomechanical properties of the artery were measured. ^ In study 1 the main changes were seen in the lipoprotein subfraction distribution. Carbohydrate restricted diet (CRD) decreased the levels of the smaller LDL particles (P < 0.001). In study 2 the CRD lowered the levels of hepatic total and esterified cholesterol, as well as ACAT activity compared to HChol (P < 0.05). In contrast dietary cholesterol downregulated HMG-CoA reductase mRNA levels (P < 0.05). ^ In study 3 CRD improved the plasma lipid profile by increasing plasma HDL-C (P < 0.05) concentrations, and by lowering the levels of both triglycerides (P < 0.01) and smaller LDL particles (P < 0.001). In contrast, dietary cholesterol affected negatively plasma lipid profile through an increase in LDL-C and total cholesterol levels (P < 0.001). CRD affected negatively hepatic lipids since it increased the liver weight and hepatic lipid accumulation (P < 0.025). In study 4 CRD reduced the aortic cytokines and the aorta stiffness. In contrast dietary cholesterol increased lipid accumulation in the aorta as well as sPLA2 activity. Summarizing the results, CRD affected positively plasma lipid metabolism and the atherosclerosis process, and had different effects in growing and adults GP in regards to hepatic lipid metabolism. ^