Metabolic controls in precancerous liver: III. Further studies on control of lipid synthesis during N-2-Fluorenylacetamide feeding

We have examined, both in vivo and in vitro, various aspects of the control of cholesterol and fatty-acid synthesis in the livers of rats fed the hepatocarcinogen, N-2-fluorenylacetamide. Within 1-4 weeks of beginning carcinogen treatment "feedback" control of cholesterol synthesis was partially or completely lost. Other controls over lipogenesis, however-fasting inhibition of cholesterol synthesis and dietary control of fatty-acid synthesis (fasting, refeeding after fasting, high-fat diet)-were retained. The normal diurnal rhythm of hepatic cholesterol synthesis was missing from carcinogen-treated animals, but this was due to an alteration in their daily pattern of voluntary food intake. The loss of "feedback" control of cholesterol synthesis was found to be not due to the reduction in food intake that accompanied carcinogen feeding. This work is further evidence in support of the hypothesis that a breakdown in "feedback" control of cholesterol synthesis is an important feature in the development of liver cancer. © 1973.