Cholesterol metabolism in ExHC (exogenous hypercholesterolemic) rats

Katsumi Imaizumi, Akihiro Nagatomi, Masao Sato, Akira Tominaga, Michihiro Sugano

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Abstract

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 < 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 β-very-low-density-lipoproteins (β-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 β-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.

Original languageEnglish
Pages (from-to)101-109
Number of pages9
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume1123
Issue number1
DOIs
Publication statusPublished - Jan 3 1992

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Endocrinology

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