Regulation of apolipoprotein B-containing lipoproteins by vitamin C level and dietary fat saturation in guinea pigs.

Effects of suboptimal and adequate vitamin C, with varying dietary fat saturation, on hepatic cholesterol and plasma lipoprotein concentrations and metabolism were studied in guinea pigs fed 15% (wt/wt) fat/0.04% cholesterol diets. Fat mixtures were either 49% saturated (SFA) (24% lauric acid) or 53% polyunsaturated fatty acid (PUFA) linoleic acid with vitamin C at 50 (suboptimal) or 500 (adequate) mg/kg diet. Guinea pigs fed suboptimal vitamin C had 15% lower hepatic active 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and 25% lower low-density lipoprotein (LDL; apolipoprotein [apo] B/E) receptor number, 20% higher acyl-CoA:cholesterol acyltransferase (ACAT) activity, 28% higher triacylglycerol (TAG) and cholesteryl ester concentrations, and increased very-low-density lipopoprotein (VLDL) apo B secretion rates in comparison to animals fed adequate vitamin C. Intake of suboptimal vitamin C lowered plasma high-density lipoprotein (HDL) cholesterol concentrations by 45% and increased plasma TAG, total and VLDL/LDL cholesterol, and cholesteryl ester transfer protein (CETP) activity by 40%, 50%, and 30%, respectively. The hyperlipidemic effects of suboptimal vitamin C were more pronounced with intake of the SFA diet. These data demonstrate that low vitamin C intake results in a pattern of changes in whole-body cholesterol and lipoprotein metabolism that are related to increased risk of cardiovascular disease (CVD).