Interactions of dietary fat type and vitamin C level on hepatic cholesterol and plasma lipoprotein metabolism.

Abstract

Effects of suboptimal and adequate vitamin C, with varying dietary fat saturation, on (i) regulation of hepatic cholesterol homeostasis, (ii) regulation of plasma lipoprotein concentrations and metabolism, and (iii) oxidative susceptibility of plasma low density lipoprotein (LDL) were studied in guinea pigs fed 15% (w/w) fat-0.04% cholesterol diets. Fat mixtures were either 50% saturated (25% lauric acid SF A):25% monounsaturated (MUFA):25% polyunsaturated (PUFA) or 25% SFA:25% MUFA:50% PUFA linoleic acid with vitamin C at 50 (suboptimal) or 500 (adequate) mg/kg diet. Intake of suboptimal vitamin C resulted in normal growth with no symptoms of scurvy. In general, independent of dietary fat saturation, significant differences were observed between suboptimal and adequate vitamin C intake on hepatic cholesterol and lipoprotein metabolism. Guinea pigs fed suboptimal vitamin C had lower hepatic vitamin C concentrations, decreased active 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase activity and LDL (apo B/E) receptor number, increased acyl-CoA:cholesterol acyltransferase (ACAT) activity, and higher hepatic triacylglycerol (TAG) and cholesteryl ester (CE) concentrations in comparison to animals fed adequate vitamin C. Intake of suboptimal vitamin C lowered plasma high density lipoprotein (HDL) cholesterol and increased plasma TAG, total and VLDLILDL cholesterol and apo B concentrations. The hyperlipidemic effects of suboptimal vitamin C were synergistic with intake of the SFA diet. LDL size, CE content, and cholesteryl ester transfer protein (CETP) activity were higher in animals fed suboptimal vitamin C. Guinea pigs fed suboptimal vitamin Chad LDL particles which were less resistant to in vitro oxidation, and lower red blood cell glutathione concentrations in comparison to animals fed adequate vitamin C. The extent ofLDL oxidation and the lowering of glutathione levels were more pronounced when suboptimal vitamin C was fed in combination with the diet high in PUF A. These results indicate that low vitamin C intake may increase risk of cardiovascular disease through changes in cholesterol and lipoprotein metabolism and the susceptibility of LDL to oxidation.