Saturated fat and simple carbohydrates elevate plasma LDL cholesterol concentrations by specific alterations on hepatic cholesterol metabolism

Abstract

We investigated the independent and interactive effects of saturated fat and simple carbohydrates on plasma and hepatic cholesterol in guinea pigs fed semipurified diets containing 19% fat ( w w ) either high in lauric + myristic (SFA), oleic (MUFA), or linoleic (PUFA) and 33.5% ( w w ) of carbohydrates either sucrose or starch for four weeks. Plasma LDL cholesterol concentrations were 40% higher in the simple carbohydrate groups compared with starch-fed animals (P <0.005). SFA-fed guinea pigs had 75% higher plasma LDL cholesterol than did those fed MUFA or PUFA diets (P< 0.0001). In addition, SFA significantly decreased HDL cholesterol levels by 100–130% compared to MUFA or PUFA diets which had similar effects. Sucrose intake resulted in increased plasma apoB concentrations compared with starch intake (P = 0.001). SFA intake also increased plasma apoB levels by 50% compared with MUFA or PUFA diets (P<0.00001). Guinea pigs fed SFA diets had 60% lower hepatic LDL receptor number than those fed MUFA and PUFA diets while sucrose intake reduced the number of hepatic LDL receptors by 30% (P < 0.01). Hepatic ACAT activity was 1.7 fold higher in animals fed sucrose diets compared with those fed starch (P<0.0001). These studies suggest that SFA and sucrose independently raise plasma LDL cholesterol levels by distinct mechanisms that alter hepatic cholesterol homeostasis and affect the synthesis and catabolism of lipoproteins.