title: SCD1 deficiency protects mice against ethanol-induced liver injury.
abstract: Stearoyl-CoA desaturase 1 (SCD1) is a delta-9 fatty acid desaturase that catalyzes the synthesis of mono-unsaturated fatty acids (MUFA). SCD1 is a critical control point regulating hepatic lipid synthesis and β-oxidation. Scd1 KO mice are resistant to the development of diet-induced non-alcoholic fatty liver disease (NAFLD). Using a chronic-binge protocol of ethanol-mediated liver injury, we aimed to determine if these KO mice are also resistant to the development of alcoholic fatty liver disease (AFLD). Mice fed a low-fat diet (especially low in MUFA) containing 5% ethanol for 10days, followed by a single ethanol (5g/kg) gavage, developed severe liver injury manifesting as hepatic steatosis. This was associated with an increase in de novo lipogenesis and inflammation. Using this model, we show that Scd1 KO mice are resistant to the development of AFLD. Scd1 KO mice do not show accumulation of hepatic triglycerides, activation of de novo lipogenesis nor elevation of cytokines or other pro-inflammatory markers. Incubating HepG2 cells with a SCD1 inhibitor induced a similar resistance to the effect of ethanol, confirming a role for SCD1 activity in mediating ethanol-induced hepatic injury. Taken together, our study shows that SCD1 is a key player in the development of AFLD and associated deleterious effects, and suggests SCD1 inhibition as a therapeutic option for the treatment of this hepatic disease.
authors.affiliation: BioMed Research Center, Biological Sciences Department, University of Quebec in Montreal, Montreal, QC H2X 1Y4, Canada.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Lounis
authors.affiliation: BioMed Research Center, Biological Sciences Department, University of Quebec in Montreal, Montreal, QC H2X 1Y4, Canada.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Escoula
authors.affiliation: BioMed Research Center, Biological Sciences Department, University of Quebec in Montreal, Montreal, QC H2X 1Y4, Canada.
authors.forename: Cathy
authors.initials: C
authors.lastname: Veillette
authors.affiliation: BioMed Research Center, Biological Sciences Department, University of Quebec in Montreal, Montreal, QC H2X 1Y4, Canada.
authors.forename: Karl-F
authors.initials: KF
authors.lastname: Bergeron
authors.affiliation: Nutritional Sciences Department, Biochemistry Department, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Ntambi
authors.affiliation: BioMed Research Center, Biological Sciences Department, University of Quebec in Montreal, Montreal, QC H2X 1Y4, Canada. Electronic address: mounier.catherine@uqam.ca.
authors.forename: Catherine
authors.initials: C
authors.lastname: Mounier
mesh_terms: D000818:Animals; D001823:Body Composition; D004032:Diet; D000431:Ethanol; D005227:Fatty Acids / Q000032:analysis; D005235:Fatty Liver, Alcoholic / Q000150:complications / Q000235:genetics / Q000473:pathology; D005247:Feeding Behavior; D017353:Gene Deletion; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000473:pathology; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000201:enzymology* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D010084:Oxidation-Reduction; D020011:Protective Agents / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D020011:Protective Agents; D000431:Ethanol; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase
keywords: Alcoholic fatty liver disease; De novo lipogenesis; Inflammation; SCD1