M. Somanchi et al., CHOLESTEROGENESIS, LIPOGENESIS, CHOLESTEROL DEGRADATION TO BILE-ACIDS, AND HISTOPATHOLOGY OF THE LIVER IN LA N-CP OBESE RATS/, Hepatology, 25(6), 1997, pp. 1451-1456
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.