Volume 89, Issue 3, March (2003), pp. 341-350 © The Author 2003
doi:10.1079/BJN2002802

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

Andrew M. Salter^1,CA, Martina A. McAteer¹, David C. Grimsditch², Martin Vidgeon-Hart³ and G. Martin Benson^2
1Division of Nutritional Biochemistry, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire LE12 5RD, UK
²Atherosclerosis Department, GlaxoSmithKline Pharmaceuticals, Harlow, Essex CM19 5AW, UK
³Safety Assessment Department, GlaxoSmithKline Pharmaceuticals, Welwyn, Hertfordshire AL6 9AR, UK

 (Received 8 April 2002–Revised 14 October 2002–Accepted 1 October 2002)

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 40g fat and 0·3g 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 150g coconut oil and either 0·5 or 5·0g 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 150g coconut oil/kg and 5·0g 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.

Abbreviations: Apo; apolipoprotein; D; diet; DNSI; dominant spot normal inbred; F; fed or fasted; HFHC; high-fat, high-cholesterol diet; HFLC; high-fat, low-cholesterol diet; LPL; lipoprotein lipase; S; strain; T; length of time on diet; TAG; triacylglycerol

Keywords:
Lipoprotein lipase, Hepatic lipase, Dominant spot normal inbred strain, Bio F₁B, Dietary cholesterol, Atherosclerosis, Hamster