Age-induced hypercholesterolemia in the rat relates to reduced elimination but not increased intestinal absorption of cholesterol.
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 whether any such age-related change could be influenced by treatment with GH or ezetimibe (EZE). Male rats aged 6 and 18 mo were studied with and without 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 (LDLRs), 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 LDLRs, 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.
Gälman
Cecilia
C
Karolinska Institute at Center for Endocrinology, Metabolism, and Diabetes, Department of Medicine and Molecular Nutrition Unit, Center for Nutrition and Toxicology, NOVUM, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Matasconi
Manuela
M
Persson
Lena
L
Parini
Paolo
P
Angelin
Bo
B
Rudling
Mats
M
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D001384:Azetidines / Q000008:administration & dosage*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D000069438:Ezetimibe; D013006:Growth Hormone / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001384:Azetidines; D001647:Bile Acids and Salts; D013006:Growth Hormone; D002784:Cholesterol; D000069438:Ezetimibe