High and low responding strains of laboratory opossums differ in sterol 27-hydroxylase and acyl-coenzyme A:cholesterol acyltransferase activities on a high cholesterol diet

Two partially inbred strains of laboratory opossums exhibit extremely high or low levels of VLDL+LDL cholesterol concentrations, respectively, when challenged with a high cholesterol and high fat diet. The present studies were conducted to determine whether the high and low responding strains differ in activities of important enzymes that have been shown to affect lipemic responsiveness to diet. We measured plasma 27-hydroxycholesterol and hepatic activities of 27-hydroxylase and 7-hydroxylase in high and low responding opossums while consuming the basal diet and cholesterol-enriched diets. Plasma 27-hydroxycholesterol concentration and 27-hydroxylase activity in liver did not differ between groups on the basal diet, but both were significantly higher in low responders than in high responders on the cholesterol-enriched diet with unsaturated fat (10.79 ± 0.56 in low vs. 7.31 ± 0.50 μg/dl in high responders for 27-hydroxycholesterol and 14.14 ± 0.79 in low vs. 10.07 ± 0.80 pmol/mg protein/min in high responders for 27-hydroxylase activity). On the other hand, 7-hydroxylase activity was significantly higher in high responding opossums (75.72 ± 6.81 pmol/mg protein/min) than in low responding opossums (51.39 ± 6.18 pmol/mg protein/min) on the basal diet, but it did not differ on the high cholesterol and high fat diet. We measured hepatic ACAT and extrahepatic hepatic 27-hydroxylase activities in high and low responding opossums on the cholesterol enriched diet. Hepatic ACAT activity was significantly higher in high responding opossums (137.00 ± 18.33 pmol/mg protein/min) than in low responding opossums (47.67 ± 2.71 pmol/mg protein/min), whereas extrahepatic 27-hydroxylase activity was higher in low responding opossums (33.00 ± 2.10 pmol/mg protein/min in lungs and 3.69 ± 0.20 in kidneys) than in high responding opossums (21.17 ± 1.54 pmol/mg protein/min in lungs and 2.82 ± 0.31 in kidneys). We also compared the composition of bile between high and low responders. The concentration of taurine conjugates of cholic acid in bile of both groups was similar, but concentration of taurine conjugates of chenodeoxycholic acid in bile of low responding animals was higher than in high responding animals (124.9 ± 17.3 in low vs. 59.2 ± 13.2 μmol/ml in high responders). The results of these studies suggest two enzymes may affect the lipemic response to diet in laboratory opossums: sterol 27-hydroxylase and ACAT. Each of these enzymes may influence diet-induced hyperlipidemia at a different step of lipoprotein metabolism.