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Journal of Lipid Research, Vol 38, 1598-1611, Copyright © 1997 by Lipid Research, Inc.
SD Turley, DK Spady and JM Dietschy
These studies were done to determine whether an underlying metabolic
difference could account for the higher concentration of cholesterol
carried in low density lipoproteins (LDL-C) in male hyperresponder (HR)
cynomolgus monkeys than in their hyporesponder (HO) counterparts during
dietary cholesterol challenge. All animals were fed to steady state at 5
months a diet that had a constant concentration of cholesterol (0.19 mg/g),
triacylglycerol (175 mg/g), and soluble fiber. There were no differences in
these two phenotypes with respect to the profile of fatty acids in the
liver and bile acids in the gallbladder, or in the relationship of
cholesterol synthesis to cholesteryl ester formation in the liver. The rate
of cholesterol synthesis in all extrahepatic tissues was also the same in
the HO and HR animals but was 2.1 mg/day per kg body weight less in the
liver of the HR monkeys. When challenged with a greater dietary cholesterol
load, therefore, the HR animal could not readily further down-regulate
synthesis and so shifted more cholesterol into the ester pool (9.4 mg/g)
than did the HO animal (3.9 mg/g). Also the LDL-C concentration was more
markedly elevated (412 mg/dl) compared to the hyporesponder monkey (188
mg/dl). Thus, this single metabolic alteration apparently accounted for the
HO and HR phenotypes. As this difference was not due to variation in the
delivery of sterol from the extrahepatic organs to the liver, it must
reflect a difference in either net intestinal sterol absorption or net
hepatic sterol excretion in the two phenotypes.
ARTICLES
Identification of a metabolic difference accounting for the hyper- and hyporesponder phenotypes of cynomolgus monkey
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 75235-8887, USA.
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