Dietary cholesterol reduces lipoprotein lipase activity in the atherosclerosis-susceptible Bio F 1 B hamster

Abstract

We have compared lipoprotein metabolism in, and susceptibility to atherosclerosis of, two strains of male Golden Syrian hamster, the Bio F 1 B 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 cholestero/g, triacylglycerol-rich lipoprotein (chylomicron+VLDL) and HDL-cholesterol were significantly higher ( P <0·001) in Bio F 1 B hamsters than DSNI hamsters. When this diet was supplemented with 150 g coconut oil and either 0·5 or 5·0 g cholestero/g, significant differences were seen in response. In particular, the high-cholesterol diet produced significantly greater increases in plasma cholesterol and triacylglycerol in the Bio F 1 B 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 oi/g and 5·0 g cholestero/g for 6 and 12 months. Again, the Bio F 1 B 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 F 1 B compared with the DSNI animals at 6 months, and virtually absent at 12 months. Bio F 1 B animals were also shown to develop significantly more ( P <0·001) atherosclerosis. These results indicate that, in the Bio F 1 B hybrid hamster, cholesterol feeding reduces lipoprotein lipase activity, thereby causing the accumulation of chylomicrons that may be associated with their increased susceptibility to atherosclerosis.