Cholesterol metabolism in ExHC (exogenous hypercholesterolemic) rats.
Exogenous hypercholesterolemic (ExHC) rats, that develop hypercholesterolemia for exogenous cholesterol, are an established strain Isolated from Sprague-Dawley (SD) rats by Imai and Matsumura ((1973) Atherosclerosis, 18, 59-64). The present study was carried out to clarify the cause of hyperresponsivity in ExHC rats to dietary cholesterol. As early as one day after feeding a high cholesterol diet (1%) serum cholesterol level was doubled in ExHC rats, while the level of hepatic cholesterol was two-thirds of SD rats. The elevation of serum cholesterol was mainly attributed to the d less than 1.006 g/ml fractions. Cholesterol feeding increased fecal bile acid excretion in both strains, but to a more greater extent in SD rats. Absorption of dietary cholesterol and synthesis of cholesterol in vivo were similar between the strains. The uptake of beta-very-low-density-lipoproteins (beta-VLDL) in vivo and the primary cultured hepatocytes was lower in ExHC rats, when a high-cholesterol diet was fed. Even without feeding of a high-cholesterol diet, preincubation with cholesterol-rich lipoproteins caused a lower association and degradation of beta-VLDL by the hepatocytes from ExHC rats. Incubation of hepatocytes with cholesterol-rich lipoproteins did not affect the secretion of [14C]cholesterol into the density less than 1.006 g/ml fraction, but suppressed the secretion into the medium density greater than 1.006 g/ml fractions. These results suggest that ExHC rats, as compared to SD rats, are defective of hepatic uptake and processing cholesterol to bile acids.
Imaizumi
K
K
Department of Food Science and Technology, School of Agriculture, Kyushu University, Fukuoka, Japan.
Nagatomi
A
A
Sato
M
M
Tominaga
A
A
Sugano
M
M
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D002791:Cholesterol, Dietary / Q000008:administration & dosage* / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005260:Female; D006937:Hypercholesterolemia / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000378:metabolism
D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D008079:Lipoproteins, VLDL; D013256:Steroids; D002784:Cholesterol