Hypocholesteremia induced by orotic acid: dietary effects and species specificity

Effects of 1% dietary orotic acid on lipid metabolism were examined in rats, mice, hamsters and guinea pigs. The influences of diet composition, age and sex on alterations induced by orotic acid were also studied. Hypocholesteremia and hepatic steatosis developed in rats fed orotic acid. These responses were little affected by dietary changes in lipid (0, 2 or 5% corn oil) or carbohydrate (high sucrose, high starch or high fiber). When included in diets containing cholesterol and cholic acid, orotic acid prevented a rise in serum cholesterol but did not maintain a normal ratio of HDL to total cholesterol. The responses of mice to orotic acid were opposite to those of rats; liver lipid was decreased, and serum cholesterol was increased. Hamsters and guinea pigs were unaffected by the compound. Thus, orotic acid is hypocholesteremic in rats, hypercholesteremic in mice and normocholesteremic in hamsters and guinea pigs. Age did not alter responses of rats to 1% dietary orotic acid. In rats and mice, sex influenced changes in hepatic lipid, with females more responsive than males.