Cholesterol synthesis in the squirrel monkey: relative rates of synthesis in various tissues and mechanisms of control

Abstract

Cholesterol synthesis has been extensively investigated in various tissues of lower mammals; however, there is little specific information concerning cholesterologenesis in the primate. Furthermore, experiments in whole animals suggest that important differences may exist in the features of cholesterologenesis in the dog and rat versus the monkey and man. Using the new world squirrel monkey, therefore, we performed the present studies to determine the rates of cholesterologenesis in various tissues per unit weight, to define the relative rates of whole organ synthesis, and to evaluate the operation of control mechanisms in these tissues. In control animals fed a low cholesterol chow diet, the liver and ileum were the two most active sites for cholesterologenesis followed, in order, by the colon, esophagus, and proximal small bowel. Rates of synthesis in 10 other tissues tested were considerably lower than these found in the gastrointestinal tract. When rates of whole organ synthesis were calculated, three tissues, i.e., liver, bowel, and skin, accounted for 92% of the total demonstrable synthetic activity. Following cholesterol feeding utilizing either a solid chow or liquid formula diet, marked suppression of hepatic cholesterologenesis occurred while synthesis in other organs remained essentially unaltered. Similarly, fasting animals for periods up to 96 hr resulted in suppression of synthesis in the liver, but not in various levels of the intestine. Finally, biliary diversion for 48 hr caused a twofold increase in hepatic cholesterologenesis and a six- to eightfold increase in sterol synthesis in the small but not the large intestine.