DECREASED RECEPTOR-MEDIATED LDL CATABOLISM IN CASEIN-FED RABBITS PRECEDES THE INCREASE IN PLASMA-CHOLESTEROL LEVELS

The effect of dietary protein on, in vivo, receptor-dependent and receptor-independent low density lipoprotein (LDL) catabolism was assessed in rabbits fed semipurified cholesterol-free diets containing casein or soy protein for 300 days. Plasma cholesterol (7.37 +/- 0.59 versus 1.84 +/- 0.28 mmol/L; P < 0.001), LDL cholesterol (2.66 +/- 0.41 versus 0.67 +/- 0.10 mmol/L; P < 0.001) and LDL apo B concentrations (1.39 +/- 0.40 versus 0.54 +/- 0.12 g/L plasma; P < 0.001) were significantly higher in rabbits fed casein. Kinetic parameters calculated following the simultaneous injection of radiolabeled native and methylated LDL showed that in casein-fed rabbits, total LDL apo B fractional catabolic rate (FCR) was significantly lower (0.64 +/- 0.11 versus 1.42 +/- 0.20 pools/d; P < 0.02), and this was due exclusively to a four-fold reduction in receptor-dependent LDL apo B FCR (0.21 +/- 0.07 versus 0.86 +/- 0.10 pools/d; P < 0.002), since receptor-independent LDL apo B FCR was similar between groups (0.44 +/- 0.05 versus 0.56 +/- 0.12 pools/d). In groups of rabbits transferred from a soy protein diet to a casein diet, total LDL apo B FCR was decreased significantly in rabbits fed casein diet, 5 days after being switched from the soy protein diet (1.03 +/- 0.08 versus 1.83 +/- 0.13 pools/d; P < 0.05). This decrease in total LDL apo B FCR was due to decreases in receptor-mediated catabolism (0.56 +/- 0.06 versus 1.03 +/- 0.14 pools/d; P < 0.001) and receptor-independent catabolism (0.47 +/- 0.09 versus 0.80 +/- 0.10 pools/d; P < 0.05). However, the plasma cholesterol in these casein-fed rabbits was not significantly different from that observed in soy protein-fed rabbits (2.33 +/- 0.52 versus 2.02 +/- 0.39 mmol/L). Compared to soy protein-fed rabbits, the plasma cholesterol was significantly higher when the casein had been fed for 10 to 25 days, and in these rabbits total LDL apo B FCR was also significantly reduced, due exclusively to decreased receptor-mediated catabolism. There was a significant inverse correlation in all rabbits between plasma cholesterol and both total LDL apo B FCR (R = 0.66; P < 0.001) and receptor-dependent LDL apo B FCR (R = 0.72; P < 0.001). These studies show that down-regulation of LDL receptors in vivo, precedes the subsequent elevation in plasma cholesterol levels induced by a casein diet.