Fatty Acid Bile Acid Conjugate Inhibits Hepatic Stearoyl Coenzyme A Desaturase and Is Non-atherogenic

Alicia Leikin-Frenkel, Ayelet Gonen, Aviv Shaish, Ilana Goldiner, Diana Leikin-Gobbi, Fred M. Konikoff, Dror Harats, Tuvia Gilat

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Aims: Suppression of stearoyl-coenzyme A desaturase (SCD) activity leads to reduction of obesity, fatty liver as well as of insulin resistance. It was, however, recently reported to enhance atherogenesis. The aim of the present study was to investigate whether inhibition of SCD by Aramchol, a fatty acid bile conjugate with known hypocholesterolemic effects, will affect atherogenesis and how. Methods: Aramchol was tested in vitro in cultured cells and in vivo in rodents. Results: Aramchol, at very low concentrations, reduced SCD activity in liver microsomes of mice. Aramchol enhanced cholesterol efflux from macrophages more than twofold. In vivo it increased fecal sterol output and decreased markedly plasma cholesterol levels in mice. In ApoE-/-, LDRL-/- and C57Bl6 mice, the effects of Aramchol on atherogenesis were non-atherogenic. Conclusions: Aramchol reduces SCD activity and is non-atherogenic. It may offer a means to obtain the desirable hepatic metabolic effects of SCD inhibition without the deleterious atherogenic effect.

Original languageEnglish
Pages (from-to)397-404
Number of pages8
JournalArchives of Medical Research
Volume41
Issue number6
DOIs
StatePublished - Aug 2010

Keywords

  • Atherosclerosis
  • Fatty acid bile acid conjugate
  • Metabolic syndrome
  • Plasma lipids
  • SCD

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