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

2009 ◽  
Vol 37 (3) ◽  
pp. 187-198 ◽  
Author(s):  
Natalia Guillén ◽  
María A. Navarro ◽  
Carmen Arnal ◽  
Enda Noone ◽  
José M. Arbonés-Mainar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Linoleic Acid ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Dna Microarrays ◽  
Hepatic Gene Expression ◽  
New Genes ◽  
Human Pathology ◽  
Cla Isomers ◽  
Deficient Mice

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.

scholarly journals Microarray analysis of hepatic genes differentially expressed in the presence of the unsaponifiable fraction of olive oil in apolipoprotein E-deficient mice

2007 ◽  
Vol 97 (4) ◽  
pp. 628-638 ◽  
Author(s):  
Sergio Acín ◽  
María A. Navarro ◽  
Javier S. Perona ◽  
Joaquín C. Surra ◽  
Natalia Guillen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Olive Oil ◽  
Genetic Background ◽  
Dna Microarrays ◽  
Biological Effects ◽  
Hepatic Gene Expression ◽  
Potential Candidate ◽  
Unsaponifiable Fraction ◽  
Olive Cultivar ◽  
Deficient Mice

The hypothesis that the unsaponifiable fraction of olive oil dramatically influences hepatic gene expression was tested in mice. Two olive oils, obtained from the same olive cultivar but by different technological procedures, were characterized to show that they differed mainly in terms of the composition/quantity of this unsaponifiable fraction. Using DNA microarrays, hepatic gene expression was analysed in apoE-deficient mice fed one of two isoenergetic, isonitrogenous diets containing either 10 % (w/w) olive oil or unsaponifiable fraction-enriched olive oil. To provide an initial screening of potential candidate genes involved in a differential response, only genes with remarkably modified expression (signal log2 ratio >3 or < − 3) were further considered. The eleven genes fulfilling these prerequisites were confirmed by quantitative RT–PCR, and then analysed in apoE-deficient mice with a C57BL/6J genetic background. Orosomucoid and serum amyloid A2 were upregulated (to variable extents depending on the genetic background) in the absence of hepatic steatosis and inflammation. Fabp5 and Mt2 were also strongly upregulated. Several proteases were highly suppressed by the unsaponifiable-enriched olive diet, independent of the genetic background. The findings indicate that change in the expression of these genes is a good marker of the intake of the unsaponifiable fraction of olive oil. The results highlight the important biological effects of the unsaponifiable fraction of olive oil. The term ‘monounsaturated fatty acid-enriched oil’ no longer appears appropriate for describing all the oils to which it is currently applied since it does not adequately reflect that they have different biological effects.

scholarly journals Effect of Lorenzo’s Oil on Hepatic Gene Expression and the Serum Fatty Acid Level in abcd1-Deficient Mice

2017 ◽  
pp. 67-74 ◽  
Author(s):  
Masashi Morita ◽  
Ayako Honda ◽  
Akira Kobayashi ◽  
Yuichi Watanabe ◽  
Shiro Watanabe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Acid Level ◽  
Hepatic Gene Expression ◽  
Fatty Acid Level ◽  
Serum Fatty Acid ◽  
Lorenzo’S Oil ◽  
Deficient Mice

An integrated reverse functional genomic and metabolic approach to understanding orotic acid-induced fatty liver

2004 ◽  
Vol 17 (2) ◽  
pp. 140-149 ◽  
Author(s):  
Julian L. Griffin ◽  
Stephanie A. Bonney ◽  
Chris Mann ◽  
Abdul M. Hebbachi ◽  
Geoff F. Gibbons ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Liver ◽  
Gene Expression Profiling ◽  
Stress Responses ◽  
Expression Profiling ◽  
Orotic Acid ◽  
Dna Microarrays ◽  
Data Sets ◽  
Functional Genomic ◽  
H Nmr

In functional genomics, DNA microarrays for gene expression profiling are increasingly being used to provide insights into biological function or pathology. To better understand the significance of the multiple transcriptional changes across a time period, the temporal changes in phenotype must be described. Orotic acid-induced fatty liver disease was investigated at the transcriptional and metabolic levels using microarrays and metabolic profiling in two strains of rats. High-resolution 1H-NMR spectroscopic analysis of liver tissue indicated that Kyoto rats compared with Wistar rats are predisposed to the insult. Metabolite analysis and gene expression profiling following orotic acid treatment identified perturbed metabolic pathways, including those involved in fatty acid, triglyceride, and phospholipid synthesis, β-oxidation, altered nucleotide, methyl donor, and carbohydrate metabolism, and stress responses. Multivariate analysis and statistical bootstrapping were used to investigate co-responses with transcripts involved in metabolism and stress responses. This reverse functional genomic strategy highlighted the relationship between changes in the transcription of stearoyl-CoA desaturase 1 and those of other lipid-related transcripts with changes in NMR-derived lipid profiles. The results suggest that the integration of 1H-NMR and gene expression data sets represents a robust method for identifying a focused line of research in a complex system.

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