REGULATORY ENZYMES OF LIPID-METABOLISM IN LA N-CP RATS/

Hepatic activities of rate limiting enzymes in fatty acid and choleste rol synthesis and cholesterol degradation were determined in lean and obese LA/N-cp rats. The hepatic activities of acetyl-CoA carboxylase a nd fatty acid synthetase, the key enzymes of fatty acid synthesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase (the rare limiting enz yme in cholesterol synthesis), were increased 2-fold in the obese rats as compared with their lean littermates. In contrast, the activity of cholesterol 7 alpha-hydroxylase, the rate limiting enzyme of choleste rol degradation to bile acids, was significantly decreased by 28% in t he obese group as compared with the control group. Significantly, comp ared with the control group, the obese animals exhibited similar magni tudes of differences in the activities of the above enzymes even when they were pair-fed with the control animals. Thus these differences in the obese group are nor due to hyperphagia but possibly to hypersecre tion of the lipogenic hormone, insulin in this strain. These results i ndicate that the LA/N-cp obese rat has twice the capacity to synthesiz e body fat and cholesterol but has a reduced capacity to degrade the c holesterol, leading to increased accumulation of cholesterol and fat.