title: Squalene in a sex-dependent manner modulates atherosclerotic lesion which correlates with hepatic fat content in apoE-knockout male mice.
abstract: BACKGROUND
  Squalene is an intermediate of cholesterol biosynthesis which can be obtained from the diet where it is abundant, for example, in olive oil. The effect of this isoprenoid on the development of atherosclerosis was investigated on apoE-knockout mice.
  
  
  RESULTS
  Two groups of animals, separated according to sex, were fed on standard chow diet: the control group receiving only vehicle and the second group an aqueous solution of squalene to provide a dose of 1g/kg/day in male and female mice. This treatment was maintained for 10 weeks. At the end of this period, plasma lipid parameters, oxidative stress markers and hepatic fat were measured as well as cross-sectional lesion area of aortic root in both groups. Data showed that in males squalene feeding reduced atherosclerotic lesion area independently of plasma lipids and activation of circulating monocytes. In contrast, squalene intake did not decrease lesion area in females, despite reducing plasma cholesterol and triglycerides, isoprostane and percentage of Mac-1 expressing white cells. In males, atherosclerotic lesion area was positively and significantly associated with hepatic fat content and the plasma triglycerides were also strongly associated with liver weight.
  
  
  CONCLUSIONS
  These results indicate that administration of squalene modulates lesion development in a gender specific manner, and that accumulation of hepatic fat by liver is highly correlated with lesion progression in males. Hence, squalene administration could be used as a safe alternative to correct hepatic steatosis and atherosclerosis particularly in males.
authors.affiliation: Departamento Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Universidad de Zaragoza, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Guillén
authors.forename: Sergio
authors.initials: S
authors.lastname: Acín
authors.forename: María A
authors.initials: MA
authors.lastname: Navarro
authors.forename: Javier S
authors.initials: JS
authors.lastname: Perona
authors.forename: José M
authors.initials: JM
authors.lastname: Arbonés-Mainar
authors.forename: Carmen
authors.initials: C
authors.lastname: Arnal
authors.forename: Alfonso J
authors.initials: AJ
authors.lastname: Sarría
authors.forename: Joaquín C
authors.initials: JC
authors.lastname: Surra
authors.forename: Ricardo
authors.initials: R
authors.lastname: Carnicer
authors.forename: Israel
authors.initials: I
authors.lastname: Orman
authors.forename: Jose C
authors.initials: JC
authors.lastname: Segovia
authors.forename: Valentina
authors.initials: V
authors.lastname: Ruiz-Gutiérrez
authors.forename: Jesús
authors.initials: J
authors.lastname: Osada
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D039481:CD11b Antigen / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004268:DNA-Binding Proteins / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D011973:Receptors, LDL / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000235:genetics; D012727:Sex Characteristics; D013185:Squalene / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: C499058:Apoa5 protein, mouse; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001057:Apolipoproteins E; D039481:CD11b Antigen; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; C075750:8-epi-prostaglandin F2alpha; D013185:Squalene; D002784:Cholesterol; D015237:Dinoprost; D043303:Aryldialkylphosphatase