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-corpulent (LA/N-cp) rats, a normotensive strain showing metabolic characteristics associated with human Type IV hyperlipidemia. Hepatic and plasma total cholesterol, high density lipoproteins (HDL) cholesterol and triglycerides were significantly higher in the obese group than in the control group. Depending upon whether the data were expressed as per 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) and 79% to 355% (P < .05), respectively, in the obese group compared with the lean control group. Similarly, hepatic rate of cholesterol synthesis was higher by 46% to 107% (P < .05) in the obese animals compared with the lean ones. In vivo hepatic rate of HDL2 cholesterol degradation 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 group nor caused by increased rate of food consumption because they were meal-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. Histopathological evaluation of the livers in the obese and control groups also showed prominent lipid droplets in the cytoplasm of the obese liver but 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 coupled with lower rate of degradation of cholesterol to bile acids.
Somanchi
M
M
DVA Medical Center, Washington, D.C. and The George Washington University, 20422, USA.
Ghosh
P
P
Redman
R S
RS
Lakshman
M R
MR
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis* / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis; D005260:Female; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000473:pathology*; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics
D001647:Bile Acids and Salts; D005227:Fatty Acids; D008055:Lipids; D002784:Cholesterol