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Physiol. Genomics 37: 187-198, 2009. First published March 3, 2009; doi:10.1152/physiolgenomics.90339.2008
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Received 23 September 2008; accepted in final form 25 February 2009.
Physiological Genomics 37:187-198 (2009)
1094-8341/09 $8.00 © 2009 American Physiological Society

Call For Papers: Comparative Genomics

Microarray analysis of hepatic gene expression identifies new genes involved in steatotic liver

Natalia Guillén 1,5, María A. Navarro 1, Carmen Arnal 2,5, Enda Noone 3, José M. Arbonés-Mainar 1, Sergio Acín 1, Joaquín C. Surra 1,5, Pedro Muniesa 4,5, Helen M. Roche 3 and Jesús Osada 1,5

1 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)
2 Departamento de Patología Animal, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain
3 Nutrigenomics Research Group, UCD Conway Institute, University College-Dublin, Belfield, Dublin, Ireland
4 Departamento de Anatomía y Embriología y Genética Animal, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza
5 CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain

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. Conclusion: 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.

conjugated linoleic acid; apolipoprotein e-deficient mice; olive oil; hepatic steatosis; DNA microarrays; Syt1






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