CHOLESTEROGENESIS, LIPOGENESIS, CHOLESTEROL DEGRADATION TO BILE-ACIDS, AND HISTOPATHOLOGY OF THE LIVER IN LA N-CP OBESE RATS/

Various lipid parameters were determined in lean control and LA/NIH-co rpulent (LA/N-cp) rats, a normotensive strain showing metabolic charac teristics associated with human Type IV hyperlipidemia. Hepatic and pl asma total cholesterol, high density Lipoproteins (HDL) cholesterol an d triglycerides were significantly higher in the obese group than in t he control group. Depending upon whether the data were expressed as pe r gram tissue or per organ, the rates of de novo fatty acid synthesis in the liver and adipose tissue were higher by 61% to 127% (P < .05) a nd 79% to 355% (P < .05), respectively, in the obese group compared wi th the lean control group. Similarly, hepatic rate of cholesterol synt hesis was higher by 46% to 107% (P < .05) in the obese animals compare d with the lean ones, In vivo hepatic rate of HDL2 cholesterol degrada tion to bile acids was lower in the obese group by 48% to 63% (P < .05 ), This was confirmed in the perfused liver in spite of the fact that cholesterol uptake from HDL2 was 3 to 4-fold higher in the obese group , These changes in lipid parameters of the obese animals were neither caused by hyperphagia because they were pair-fed with the control grou p nor caused by increased rate of food consumption because they were m eal-fed, At the same time, all these lipid parameters were 17% to 20% higher in ad libitum-fed obese than in pair-fed obese group. Histopath ological evaluation of the livers in the obese and control groups also showed prominent lipid droplets in the cytoplasm of the obese liver b ut not in the lean control liver. Thus, the possible causes of obesity in the LA/N-cp obese rats are higher synthetic rates of lipids couple d with lower rate of degradation of cholesterol to bile acids.