in the obese strain. 6 Our ongoing studies 7 clearly showed that Various lipid parameters were determined in lean conthe activities of key regulatory enzymes involved in fatty trol and LA/NIH-corpulent (LA/N-cp) rats, a normotenacid and cholesterol synthesis, namely, acetyl coenzyme A sive strain showing metabolic characteristics associated carboxylase, fatty acid synthetase and 3-hydroxy-3-methylwith human Type IV hyperlipidemia. Hepatic and glutaryl coenzyme A reductase were markedly increased, plasma total cholesterol, high density lipoproteins whereas the activity of cholesterol 7a-hydroxylase, the rate (HDL) cholesterol and triglycerides were significantly limiting enzyme in the degradation of cholesterol to bile higher in the obese group than in the control group.acids, was decreased in the corpulent obese strain of rat as Depending upon whether the data were expressed as compared with its lean counterpart. per gram tissue or per organ, the rates of de novo fattyIn an attempt to see whether these findings with the lipoacid synthesis in the liver and adipose tissue were genic and cholesterol degradative enzymes are supported by higher by 61% to 127% (P õ .05) and 79% to 355% (P õ in vivo data, the present study was undertaken to determine .05), respectively, in the obese group compared with the the following parameters in the obese and lean LA/N-cp rat: lean control group. Similarly, hepatic rate of cholesterol 1) the liver and plasma cholesterol and triglycerides, includsynthesis was higher by 46% to 107% (P õ .05) in the ing plasma high density lipoprotein (HDL) cholesterol, 2) abobese animals compared with the lean ones. In vivo hesolute rates of hepatic fatty acid in the liver and adipose patic rate of HDL 2 cholesterol degradation to bile acids tissue and hepatic cholesterol synthesis using tritiated water, was lower in the obese group by 48% to 63% (P õ .05).3) in vivo hepatic rate of HDL 2 cholesterol degradation to bile This was confirmed in the perfused liver in spite of the acids, 4) in vitro hepatic uptake of cholesterol from HDL 2 and fact that cholesterol uptake from HDL 2 was 3-to 4-fold its degradation to bile acids, and 5) correlation of these rehigher in the obese group. These changes in lipid paramsults with histopathological changes in the liver. A previous eters of the obese animals were neither caused by hyperstudy 8 showed the existence of sexual dimorphism in LA/N phagia because they were pair-fed with the control corpulent strain, with the female showing much higher very group nor caused by increased rate of food consumption low density lipoprotein and hyperlipidemia than the males. because they were meal-fed. At the same time, all these Therefore, we chose LA/N females for this study. lipid parameters were 17% to 20% higher in ad libitumfed obese than in pair-fed obese group. Histopathologi-
MATERIALS AND METHODScal evaluation of the livers in the obese and control groups also showed prominent lipid droplets in the cyto- in obese LA/cp rats have been reported. 5 The increased levels...
