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.
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.
Authors: Dipankar Bhattacharya; Brittany Basta; Jose M Mato; Amanda Craig; David Fernández-Ramos; Fernando Lopitz-Otsoa; Darya Tsvirkun; Liat Hayardeny; Vasuretha Chandar; Robert E Schwartz; Augusto Villanueva; Scott L Friedman Journal: JHEP Rep Date: 2021-01-28
Authors: David Fernández-Ramos; Fernando Lopitz-Otsoa; Laura Delacruz-Villar; Jon Bilbao; Martina Pagano; Laura Mosca; Maider Bizkarguenaga; Marina Serrano-Macia; Mikel Azkargorta; Marta Iruarrizaga-Lejarreta; Jesús Sot; Darya Tsvirkun; Sebastiaan Martijn van Liempd; Felix M Goni; Cristina Alonso; María Luz Martínez-Chantar; Felix Elortza; Liat Hayardeny; Shelly C Lu; José M Mato Journal: World J Gastroenterol Date: 2020-09-14 Impact factor: 5.742
Authors: Marta Iruarrizaga-Lejarreta; Marta Varela-Rey; David Fernández-Ramos; Ibon Martínez-Arranz; Teresa C Delgado; Jorge Simon; Virginia Gutiérrez-de Juan; Laura delaCruz-Villar; Mikel Azkargorta; José L Lavin; Rebeca Mayo; Sebastiaan M Van Liempd; Igor Aurrekoetxea; Xabier Buqué; Donatella Delle Cave; Arantza Peña; Juan Rodríguez-Cuesta; Ana M Aransay; Felix Elortza; Juan M Falcón-Pérez; Patricia Aspichueta; Liat Hayardeny; Mazen Noureddin; Arun J Sanyal; Cristina Alonso; Juan Anguita; María Luz Martínez-Chantar; Shelly C Lu; José M Mato Journal: Hepatol Commun Date: 2017-10-04