title: Proteomics and gene expression analyses of mitochondria from squalene-treated apoE-deficient mice identify short-chain specific acyl-CoA dehydrogenase changes associated with fatty liver amelioration.
abstract: Squalene, a hydrocarbon involved in cholesterol biosynthesis, is an abundant component in virgin olive oil. Previous studies showed that its administration decreased atherosclerosis and steatosis in male apoE knock-out mice. To study the effect of squalene on mitochondrial proteins in fatty liver, 1 g/kg/day of this isoprenoid was administered to those mice. After 10 weeks, hepatic fat was assessed and protein extracts from mitochondria enriched fractions from control and squalene-treated animals were analyzed by 2D-DIGE. Spots exhibiting significant differences were identified by MS analysis. Squalene administration modified the expression of eighteen proteins involved in different metabolic processes, 12 associated with hepatic fat content. Methionine adenosyltransferase I alpha (Mat1a) and short-chain specific acyl-CoA dehydrogenase (Acads) showed significant increased and decreased transcripts, respectively, consistent with their protein changes. These mRNAs were also studied in wild-type mice receiving squalene, where Mat1a was found increased and Acads decreased. However, this mRNA was significantly increased in the absence of apolipoprotein E. These results suggest that squalene action may be executed through a complex regulation of mitochondrial protein expression, including changes in Mat1a and Acads levels. Indeed, Mat1a is a target of squalene administration while Acads reflects the anti-steatotic properties of squalene.
authors.affiliation: Departamento Bioquímica y Biología Molecular y Celular, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, Spain.
authors.forename: Adela
authors.initials: A
authors.lastname: Ramírez-Torres
authors.forename: Sílvia
authors.initials: S
authors.lastname: Barceló-Batllori
authors.forename: Erika
authors.initials: E
authors.lastname: Fernández-Vizarra
authors.forename: María A
authors.initials: MA
authors.lastname: Navarro
authors.forename: Carmen
authors.initials: C
authors.lastname: Arnal
authors.forename: Natalia
authors.initials: N
authors.lastname: Guillén
authors.forename: Sergio
authors.initials: S
authors.lastname: Acín
authors.forename: Jesús
authors.initials: J
authors.lastname: Osada
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D044926:Butyryl-CoA Dehydrogenase / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008716:Methionine Adenosyltransferase / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D013185:Squalene / Q000494:pharmacology; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D001057:Apolipoproteins E; D012333:RNA, Messenger; D013185:Squalene; D044926:Butyryl-CoA Dehydrogenase; C490703:Mat1a protein, mouse; D008716:Methionine Adenosyltransferase