The Golden Syrian hamster (Mesocricetus auratus) has been shown to be a useful model of both human lipoprotein metabolism and the development of atherosclerosis. We report the effects of dietary lipids on the progression and regression of atherosclerosis in this model. In the first study, hamsters fed on coconut oil (150 g/kg diet) and cholesterol (30 g/kg diet) developed lipid-rich lesions in the ascending aorta (0⋅28 (SD 0⋅14) mm 2 ) and aortic arch (0⋅01 (SD 0⋅01) mm 2 ) after 4 weeks that continued to progress over the next 8 weeks (0⋅75 (SD 0⋅41) mm 2 and 0⋅12 (SD 0⋅11) mm 2 for the ascending aorta and aortic arch respectively). Removal of cholesterol from the diet halted this progression. Furthermore, in animals fed on olive oil in the absence of added cholesterol, plasma LDL-cholesterol concentrations were lower (P Ͻ 0⋅05) and the extent of atherosclerotic lesions was reduced (P Ͻ 0⋅001 for both regions of the aorta) compared with animals fed on coconut oil (with no added cholesterol). In a second study, animals were fed on the atherogenic diet for 10 weeks, transferred to diets containing either coconut oil (150 g/kg diet) or olive oil (150 g/kg diet) without added cholesterol and monitored for up to 16 weeks. In the ascending aorta, lesion size doubled in animals fed on coconut oil but stabilized in those fed on olive oil. In the aortic arch, lesion size decreased linearly (P Ͻ 0⋅05, P Ͻ 0⋅001 for coconut oil and olive oil respectively) with the greatest reduction being seen in the olive-oil-fed animals (P Ͻ 0⋅05). Again, progression and regression of atherosclerosis appeared to reflect the relative concentrations of LDL-cholesterol and HDL-cholesterol in the plasma. We conclude that the male Golden Syrian hamster represents a useful model of dietary induced regression as well as progression of atherosclerosis. Hamster: Atherosclerosis: Coconut oil: Olive oil: Dietary fatThe Golden Syrian hamster (Mesocricetus auratus) has been used extensively in studies of lipoprotein metabolism.

Hepatic Mg2 + -dependent phosphatidate phosphohydrolase (PAP-I) is involved in the de now synthesis of triacylglycerols, phosphatidylcholine and phosphatidylethanolamine. The biosynthesis of phospholipids takes precedence over that of triacylglycerols when the rate of synthesis of diacylglycerol is low. This ensures that membrane turnover and bile secretion are maintained. PAP-1 is located in the cytosol but for metabolic function it translocates to the endoplasmic reticulum. Such translocation is stimulated by high intrecellular fatty acid concentrations and this is believed to be a major point of regulation of the synthesis of hiacylglycerol and phospholipids Ill.Considerable interest has been centred on the hamster as a model for studying lipoprotein metabolism. This is because cholesterol metabolism in this species resembles that of humans in a number of respects, including the respoase to dietary cholesterol and fat 121. Far less interest has focused on Eriacylglycerol metabolism. although Ontko et al I31 have reported an apparent hypertriglyceridaemia in hamsters, relative to rats. This isassociated w i t h iacreased incorporation of nonesterified fatty acids into triacylglycerol and increased hepatic production of VLDL. In the present study we have looked at the effect of dietary cholesterol on plasma VLDL concentrations and the activity of PAP-1.24 Male Golden Syrian hamsters, 3-4 months old, were fed diets containing O,O.M,O. 12 or 0.24% (wlw) cholesterol, for 28 days. At the end of the trial, fasting blood was collected by cardiac plncture and livers were removed and frozen prior to measuring PAP-1 activity. Lipoproteins were separated from serum by preparative ultracentrifugation and VLDL cholesterol and triacylglycerol was measured enzymatically. Serum nonesterified fatty acids were also measured by an enzymatic method. PAP-I activity was measured by the method of Martin et a1 141 and is defmed as n-ethylmaleimide sensitive, Mg2+ -Stimulated PAP activity. Table 1 summarizes our findings. A strong correlation was found between VLDL triacylglycerol concentrations and dietary cholesterol (r = 0.981). Further correlations were also seen between dietary cholesterol and serum non-esterified fatty acids (r = 0.999) and hepatic PAP-1 (r = 0.971). VLDL triacylglycerol and PAP-I were also highly correlated (r = 0.861).Finally, a strong correlation between VLDL cholesterol and triacylglycerol was also found (r = 0.977).These results suggest that cholesterol feeding induces hypertriglyceridemia in hamsters. This i?mease in serum VLDL triacylglycerol is associated with increases in serum nonesterified fatty acids and hepatic PAP-I activity. The reason for the increase in non-esterified fatty acids is unclear. It may be that cholesterol feeding induces an insulin resistant state and that this results in increased lipolytic activity in adipose tissue. It seems likely that PAP-I activity is increased in response to the elevated fatty acid levels and this results in increased synthesis and secretion of triacylglycerol...