Evidence that the major oxysterols in human circulation originate from distinct pools of cholesterol: A stable isotope study

Steve Meaney, Moustapha Hassan, Augustinas Sakinis, Dieter Lütjohann, Klaus Von Bergmann, Åke Wennmalm, Ulf Diczfalusy, Ingemar Björkhem

Research output: Contribution to journalArticlepeer-review

Abstract

The major oxysterols in human circulation are 7α-, 27-, and (24S)-hydroxycholesterol. Two unique experiments were performed to elucidate their origin and kinetics. A volunteer was exposed to 18O2-enriched air. A rapid incorporation of 18O in both 7α- and 27-hydroxycholesterol and disappearance of label after exposure were observed. The half-life was estimated to be less than 1 h. Incorporation of 18O in (24S)-hydroxycholesterol was not significant. In the second experiment a volunteer was infused with liposomes containing 10 g of [2H6]cholesterol. This resulted in an enrichment of plasma cholesterol with 2H of up to 13%, and less than 0.5% in cerebrospinal fluid cholesterol. The content of 2H in circulating 7α-hydroxycholesterol remained approximately equal to that of plasma cholesterol and decreased with a half-life of about 13 days. The 2H content of circulating 27-hydroxycholesterol was initially lower than that of cholesterol but in the last phase of the experiment it exceeded that of cholesterol. No significant incorporation of 2H in (24S)-hydroxycholesterol was observed. It is evident that 7α-hydroxycholesterol must originate from a rapidly miscible pool, about 80% of 27-hydroxycholesterol from a more slowly exchangeable pool, and more than 90% of (24S)-hydroxycholesterol from a nonexchangeable pool, presumably the brain. The results are discussed in relation to the role of oxysterols in cholesterol homeostasis and their use as markers for pathological conditions. - Meaney, S., M. Hassan, A. Sakinis, D. Lütjohann, K. von Bergmann, Å. Wennmalm, U. Diczfalusy, and I. Björkhem. Evidence that the major oxysterols in human circulation originate from distinct pools of cholesterol: a stable isotope study.

Original languageEnglish
Pages (from-to)70-78
Number of pages9
JournalJournal of Lipid Research
Volume42
Issue number1
Publication statusPublished - 2001
Externally publishedYes

Keywords

  • Brain cholesterol
  • CYP27
  • CYP46
  • CYP7A
  • O study

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