1. Plasma levels of 24S-hydroxycholesterol reflect the balance between cerebral production and hepatic metabolism and are inversely related to body surface
- Author
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Gösta Eggertsen, Ulf Diczfalusy, Lutz Bindl, Lars Ståhle, Ingemar Björkhem, Dieter Lütjohann, Lionel Bretillon, Torulf Widhe, Unité mixte de recherche nutrition lipidique et régulation fonctionnelle du coeur et des vaisseaux, Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11), Rheinische Friedrich-Wilhelms-Universität Bonn, and Karolinska Institutet [Stockholm]
- Subjects
Male ,Aging ,Body Surface Area ,[SDV]Life Sciences [q-bio] ,Biochemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,polycyclic compounds ,Child ,liver volume ,ComputingMilieux_MISCELLANEOUS ,Aged, 80 and over ,Body surface area ,0303 health sciences ,cholesterol 24S-hydroxylase ,Chemistry ,Brain ,cholestérol ,Middle Aged ,foie ,système nerveux central ,Liver ,brain size ,Child, Preschool ,Female ,lipids (amino acids, peptides, and proteins) ,composition du sang ,Adult ,medicine.medical_specialty ,Adolescent ,Oxysterol ,QD415-436 ,03 medical and health sciences ,stérol ,Internal medicine ,Body surface ,medicine ,Humans ,hydroxycholestérol ,Cholesterol 24-hydroxylase ,métabolisme ,Aged ,030304 developmental biology ,Balance (ability) ,Cholesterol ,Infant ,plasma sanguin ,Cell Biology ,Plasma levels ,Hydroxycholesterols ,brain cholesterol homeostasis ,030217 neurology & neurosurgery ,Drug metabolism - Abstract
We have previously presented evidence that most of the 24S-hydroxycholesterol present in the circulation originates from the brain and that most of the elimination of this oxysterol occurs in the liver. Plasma 24S-hydroxycholesterol levels decline by a factor of about 5 during the first decades of life. The concentration of the enzyme cholesterol 24S-hydroxylase in the brain is, however, about constant from the first year of life, and reduced enzyme levels thus cannot explain the decreasing plasma levels during infancy. In the present work we tested the hypothesis that the plasma levels of 24S-hydroxycholesterol may reflect the size of the brain relative to the capacity of the liver to eliminate the substance. It is shown here that the age-dependent changes in absolute as well as cholesterol-related plasma level of 24S-hydroxycholesterol closely follow the changes in the ratio between estimated brain weight and estimated liver volume. The size of the brain is increased only about 50% whereas the size of the liver is increased by about 6-fold after the age of 1 year. Liver volume is known to be highly correlated to body surface, and in accordance with this the absolute as well as the cholesterol-related plasma level of 24S-hydroxycholesterol was found to be highly inversely correlated to body surface in 77 healthy subjects of varying ages (r2 = 0.74). Two chondrodystrophic dwarves with normal size of the brain but with markedly reduced body area had increased levels of 24S-hydroxycholesterol when related to age but normal levels when related to body surface. It is concluded that the balance between cerebral production and hepatic metabolism is a critical determinant for plasma levels of 24S-hydroxycholesterol at different ages and that endocrinological factors are less important. The results are discussed in relation to the possibility to use 24S-hydroxycholesterol in the circulation as a marker for cholesterol homeostasis in the brain.—Bretillon, L., D. Lütjohann, L. Ståhle, T. Widhe, L. Bindl, G. Eggertsen, U. Diczfalusy, and I. Björkhem. Plasma levels of 24S-hydroxycholesterol reflect the balance between cerebral production and hepatic metabolism and are inversely related to body surface. J. Lipid Res. 2000. 41: 840–845.
- Published
- 2000