Dietary cholesterol reduces lipoprotein lipase activity in the atherosclerosis-susceptible Bio F1B hamster

We have compared lipoprotein metabolism in, and susceptibility to atherosclerosis of, two strains of male Golden Syrian hamster, the Bio F1B hybrid and the dominant spot normal inbred (DSNI) strain. When fed a normal low-fat diet containing approximately 40 g fat and 0.3 g cholesterol/kg, triacylglycerol-rich lipoprotein (chylomicron+VLDL) and HDL-cholesterol were significantly higher (P<0.001) in Bio F1B hamsters than DSNI hamsters. When this diet was supplemented with 150 g coconut oil and either 0.5 or 5.0 g cholesterol/kg, significant differences were seen in response. In particular, the high-cholesterol diet produced significantly greater increases in plasma cholesterol and triacylglycerol in the Bio F1B compared with the DSNI animals (P=0.002 and P<0.001 for cholesterol and triacylglycerol, respectively). This was particularly dramatic in non-fasting animals, suggesting an accumulation of chylomicrons. In a second experiment, animals were fed 150 g coconut oil/kg and 5.0 g cholesterol/kg for 6 and 12 months. Again, the Bio F1B animals showed dramatic increases in plasma cholesterol and triacylglycerol, and this was confirmed as primarily due to a rise in chylomicron concentration. Post-heparin lipoprotein lipase activity was significantly reduced (P<0.001) in the Bio F1B compared with the DSNI animals at 6 months, and virtually absent at 12 months. Bio F1B animals were also shown to develop significantly more (P<0.001) atherosclerosis. These results indicate that, in the Bio F1B hybrid hamster, cholesterol feeding reduces lipoprotein lipase activity, thereby causing the accumulation of chylomicrons that may be associated with their increased susceptibility to atherosclerosis.