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Am J Physiol Endocrinol Metab (June 19, 2007). doi:10.1152/ajpendo.00166.2007
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Submitted on March 14, 2007
Accepted on June 13, 2007

The age-induced hypercholesterolemia in the rat relates to reduced elimination but not increased intestinal absorption of cholesterol

Cecilia Galman1, Manuela Matasconi1, Lena Persson1, Paolo Parini1, Bo Angelin1, and Mats Rudling1*

1 Karolinska Institute, Dept of Medicine, Stockholm, Sweden

* To whom correspondence should be addressed. E-mail: mats.rudling{at}cnt.ki.se.

Plasma cholesterol increases in normal aging in both rodents and humans. This is associated with reduced elimination of cholesterol as bile acids (BAs) and decreased receptor-mediated clearance of plasma LDL, changes that can be reversed by treatment with growth hormone (GH). The level of intestinal absorption of cholesterol may also contribute to the development of hypercholesterolemia. In this study we investigated whether cholesterol absorption increases with age, and if any such age-related change could be influenced by treatment with GH or ezetimibe (EZE). Male rats, 6 and 18 months, were studied +/- GH or EZE treatment. BA synthesis was reduced and plasma cholesterol was increased in the old animals, whereas cholesterol absorption was unaltered. Cholesterol absorption was not altered by GH treatment but was reduced by EZE in both groups of animals. Hepatic LDL-receptors, scavenger receptor-class B type 1 and proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) transcripts were unchanged in old animals. GH treatment induced LDLR, PCSK9 transcripts and BA synthesis. We conclude that the age-induced hypercholesterolemia in the rat and its reversal by GH treatment relates to altered degradation of cholesterol in the liver and is not due to changes in cholesterol absorption.




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