Fatty acid bile acid conjugate inhibits hepatic stearoyl coenzyme A desaturase and is non-atherogenic.
OBJECTIVE
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.
Minerva Center for Cholesterol Gallstones and Lipid Metabolism in the Liver, Tel-Aviv University, Tel-Aviv, Israel.
Alicia
A
Leikin-Frenkel
Ayelet
A
Gonen
Aviv
A
Shaish
Ilana
I
Goldiner
Diana
D
Leikin-Gobbi
Fred M
FM
Konikoff
Dror
D
Harats
Tuvia
T
Gilat
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology*; D002784:Cholesterol / Q000378:metabolism; D002793:Cholic Acids / Q000494:pharmacology*; D006224:Cricetinae; D004036:Diet, Atherogenic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors*
D001057:Apolipoproteins E; D002793:Cholic Acids; D004791:Enzyme Inhibitors; D011973:Receptors, LDL; D002784:Cholesterol; D013230:Stearoyl-CoA Desaturase; C455117:aramchol