TY - JOUR
T1 - Role of liver in the synthesis of cholesterol and the clearance of low density lipoproteins in the cynomolgus monkey
AU - Turley, S. D.
AU - Spady, D. K.
AU - Dietschy, J. M.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1995
Y1 - 1995
N2 - The suitability of the adult male cynomolgus monkey as a model for investigating genetic mechanisms that regulate dietary cholesterolemic response was evaluated by carrying out a systematic characterization of the major aspects of cholesterol metabolism in this species. In monkeys maintained on a diet enriched with saturated fat but low in cholesterol (0.019%, wt/wt), plasma total and low density lipoprotein cholesterol (LDL- C) concentrations were 118 ± 6 and 45.3 ± 34 mg/dl, respectively. Intestinal cholesterol absorption averaged 54.0 ± 2.5%, and the rate of whole body sterol synthesis was 10.8 ± 0.6 mg/day per kg body weight. Only 11.2 ± 2.6% of this synthesis occurred in the liver. In contrast, the liver was the major site for low density lipoprotein clearance accounting for almost 80% of LDL-C degradation in these animals. The liver, which represented 1.5% of whole body mass, had a total and esterified cholesterol concentration of 4.95 ± 0.29 and 2.05 ± 0.30 mg/g, respectively. When challenged with a matching high cholesterol diet (0.19%, wt/wt), the monkeys developed marked hypercholesterolemia that was accounted for mainly by a 7- fold increase in the LDL-C levels. There was, however, wide individual variation among the monkeys in the magnitude of their cholesterolemic response. Hepatic total and esterified cholesterol levels increased 2.5- anti 4.6-fold, respectively. Comparative experiments showed that while several of the metabolic characteristics of this species of monkey were similar to those found in the hamster, they were generally very different from those seen in the rat. Thus, the male cynomolgus monkey has many characteristics in common with humans and represents an attractive model for further delineating the genetic mechanisms that dictate variable responsiveness to dietary cholesterol and triacylglycerol.
AB - The suitability of the adult male cynomolgus monkey as a model for investigating genetic mechanisms that regulate dietary cholesterolemic response was evaluated by carrying out a systematic characterization of the major aspects of cholesterol metabolism in this species. In monkeys maintained on a diet enriched with saturated fat but low in cholesterol (0.019%, wt/wt), plasma total and low density lipoprotein cholesterol (LDL- C) concentrations were 118 ± 6 and 45.3 ± 34 mg/dl, respectively. Intestinal cholesterol absorption averaged 54.0 ± 2.5%, and the rate of whole body sterol synthesis was 10.8 ± 0.6 mg/day per kg body weight. Only 11.2 ± 2.6% of this synthesis occurred in the liver. In contrast, the liver was the major site for low density lipoprotein clearance accounting for almost 80% of LDL-C degradation in these animals. The liver, which represented 1.5% of whole body mass, had a total and esterified cholesterol concentration of 4.95 ± 0.29 and 2.05 ± 0.30 mg/g, respectively. When challenged with a matching high cholesterol diet (0.19%, wt/wt), the monkeys developed marked hypercholesterolemia that was accounted for mainly by a 7- fold increase in the LDL-C levels. There was, however, wide individual variation among the monkeys in the magnitude of their cholesterolemic response. Hepatic total and esterified cholesterol levels increased 2.5- anti 4.6-fold, respectively. Comparative experiments showed that while several of the metabolic characteristics of this species of monkey were similar to those found in the hamster, they were generally very different from those seen in the rat. Thus, the male cynomolgus monkey has many characteristics in common with humans and represents an attractive model for further delineating the genetic mechanisms that dictate variable responsiveness to dietary cholesterol and triacylglycerol.
KW - bile acid
KW - cholesterol synthesis
KW - cholesteryl esters
KW - dietary cholesterolemic response
KW - genetic regulation
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M3 - Article
C2 - 7706949
AN - SCOPUS:0028833385
SN - 0022-2275
VL - 36
SP - 67
EP - 79
JO - Journal of lipid research
JF - Journal of lipid research
IS - 1
ER -