Vitamin C level and dietary fat saturation alter hepatic cholesterol homeostasis and plasma LDL metabolism in guinea pigs

This study addressed the independent and inter active effects of vitamin C status and dietary fat saturation on hepatic cholesterol and LDL metabolism in guinea pigs. Animals were fed adequate (500 mg/kg) or marginal (50 mg/kg) vitamin C with diets high in polyunsaturated (POLY), monounsaturated (MONO), or saturated (SAT)fatty acids during 6 weeks. Plasma cholesterol, triacylglycerol (TAG), and apo B concentrations were higher in animals fed vitamin C-deficient compared with Vit C-adequate diets (P < 0.02). SAT fat intake also resulted in more elevated plasma cholesterol and apo B concentrations (P < 0.001). The susceptibility of LDL to oxidation was highest in animals fed POLY diets and marginal levels of vitamin C (P < 0.001). Intake of adequate levels of vitamin C significantly reduced TBARS formation by 64% in animals fed POLY diets indicating an interactive effect between POLY fat intake and the level of vitamin C. Hepatic Acyl CoA cholesterol acyltransferase (ACAT) activity was higher by SAT fat intake (P < 0.01) and marginal intake of vitamin C (P < 0.05), whereas cholesterol 7α-hydroxylase activity was lower in vitamin C-deficient groups (P < 0.01). LDL fractional catabolic rates (FCR) were 42 to 67% faster and LDL apo B flux slower in animals fed POLY and MONO diets compared with the SAT group (P < 0.001). Animals fed marginal levels of vitamin C had higher LDL apo B flux (P < 0.05). These data suggest that the higher plasma LDL concentrations induced by SAT diets are caused by both slower LDL FCR and higher LDL apo B flux, whereas the hypercholesterolemia and hypertriglyceridemia induced by vitamin C deficiency with POLY and MONO diets is mainly caused by alterations in hepatic cholesterol homeostasis, which result in higher LDL apo B flux.