Microarray analysis of hepatic gene expression identifies new genes involved in steatotic liver.
Trans-10, cis-12-conjugated linoleic acid (CLA)-enriched diets promote fatty liver in mice, while cis-9, trans-11-CLA ameliorates this effect, suggesting regulation of multiple genes. To test this hypothesis, apoE-deficient mice were fed a Western-type diet enriched with linoleic acid isomers, and their hepatic gene expression was analyzed with DNA microarrays. To provide an initial screening of candidate genes, only 12 with remarkably modified expression between both CLA isomers were considered and confirmed by quantitative RT-PCR. Additionally mRNA expression of 15 genes involved in lipid metabolism was also studied. Ten genes (Fsp27, Aqp4, Cd36, Ly6d, Scd1, Hsd3b5, Syt1, Cyp7b1, and Tff3) showed significant associations among their expressions and the degree of hepatic steatosis. Their involvement was also analyzed in other models of steatosis. In hyperhomocysteinemic mice lacking Cbs gene, only Fsp27, Cd36, Scd1, Syt1, and Hsd3b5 hepatic expressions were associated with steatosis. In apoE-deficient mice consuming olive-enriched diet displaying reduction of the fatty liver, only Fsp27 and Syt1 expressions were found associated. Using this strategy, we have shown that expression of these genes is highly associated with hepatic steatosis in a genetic disease such as Cbs deficiency and in two common situations such as Western diets containing CLA isomers or a Mediterranean-type diet.


CONCLUSIONS
The results highlight new processes involved in lipid handling in liver and will help to understand the complex human pathology providing new proteins and new strategies to cope with hepatic steatosis.
Guillén
Natalia
N
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto Aragonés de Ciencias de la Salud (Universidad de Zaragoza-Salud del Gobierno de Aragón), Spain.
Navarro
María A
MA
Arnal
Carmen
C
Noone
Enda
E
Arbonés-Mainar
José M
JM
Acín
Sergio
S
Surra
Joaquín C
JC
Muniesa
Pedro
P
Roche
Helen M
HM
Osada
Jesús
J
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D000072474:Cytochrome P450 Family 7; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020690:GTPase-Activating Proteins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D020022:Genetic Predisposition to Disease / Q000235:genetics; D007536:Isomerism; D019787:Linoleic Acid / Q000008:administration & dosage / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism
D001057:Apolipoproteins E; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D018955:CD36 Antigens; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D011506:Proteins; C504363:TBC1D15 protein, mouse; C525805:fat-specific protein 27, mouse; D019787:Linoleic Acid; D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C097207:Cyp7b1 protein, mouse; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D003541:Cystathionine beta-Synthase