Cholesterol absorption and hepatic acyl-coenzyme A: Cholesterol acyltransferase activity play major roles in lipemic response to dietary cholesterol and fat in laboratory opossums

Partially inbred lines of laboratory opossums differ considerably in their low-density lipoprotein (LDL) cholesterol responses to dietary cholesterol and fat. Genetic analysis suggested that a single major gene is responsible for the variation in LDL cholesterol on the high cholesterol and high fat (HCHF) diet. We measured cholesterol absorption and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in intestine and liver to narrow the search for the major gene. We measured plasma lipoproteins and percent cholesterol absorption by the fecal isotope ratio method in high and low responding lines of opossums on basal and HCHF diets. We also measured lipids in liver and ACAT activity in liver and intestine on the HCHF diet. High and low lines exhibited no differences in percent cholesterol absorption on the basal diet. However, high responding opossums had significantly higher percent cholesterol absorption, hepatic free and esterified cholesterol, and hepatic ACAT activity than low responding opossums on the HCHF diet. Hepatic ACAT activity but not the intestinal ACAT activity was associated with hepatic cholesterol concentration and percent cholesterol absorption. Cholesterol absorption is a major determinant of diet-induced hyperlipidemia in opossums. Hepatic ACAT activity but not the intestinal ACAT may also play a role in diet-induced hyperlipidemia in opossums.