Synthesis of long-chain polyunsaturated fatty acids is inhibited in vivo in hypercholesterolemic rabbits and in vitro by oxysterols

P. Risé, M. Camera, D. Caruso, S. Ghezzi, F. Visioli, C. Galli

Research output: Contribution to journalArticle

Abstract

Plasma total lipids, total cholesterol (cholesterol esters and free cholesterol) and oxysterol (mainly 7β-hydroxycholesterol (7β OH)) concentrations were significantly elevated in New Zealand rabbits fed a 2% cholesterol-containing diet with respect to controls fed the same diet without cholesterol. In addition, linoleic (18:2 n-6) and α-linolenic acid (18:3 n-3) plasma concentrations were significantly elevated in hypercholesterolemic rabbits, while concentrations of long-chain n-6 and n-3 derivatives were reduced. Studies in monocytic cell line THP-1 revealed that 7β OH markedly inhibited the conversion of 18:2 to 20:4 n-6 and of 18:3 to 22:6 n-3, indicating depression of the desaturation steps; in particular the inhibition was greater for the Δ5 desaturation step. Furthermore, experiments of Real-Time PCR showed that 5-10μM 7β OH decreased the Δ5 gene expression. In conclusion, atherogenic oxysterols interfere with the production of long-chain polyunsaturated fatty acids from their precursors both in hypercholesterolemic rabbits and in cultured cells.

Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalProstaglandins, Leukotrienes and Essential Fatty Acids
Volume71
Issue number2
DOIs
Publication statusPublished - Aug 2004

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Keywords

  • Δ5 desaturase
  • Fatty acids
  • Hypercholesterolemic rabbits
  • Oxysterols
  • THP-1 cells

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism

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