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Transcriptome profiling of the feeding-to-fasting transition in chicken liver

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      Abstract

      Background

      Starvation triggers a complex array of adaptative metabolic responses including energy-metabolic responses, a process which must imply tissue specific alterations in gene expression and in which the liver plays a central role. The present study aimed to describe the evolution of global gene expression profiles in liver of 4-week-old male chickens during a 48 h fasting period using a chicken 20 K oligoarray.

      Results

      A large number of genes were modulated by fasting (3532 genes with a pvalue corrected by Benjamini-Hochberg < 0.01); 2062 showed an amplitude of variation higher than +/- 40% among those, 1162 presented an human ortholog, allowing to collect functional information. Notably more genes were down-regulated than up-regulated, whatever the duration of fasting (16 h or 48 h). The number of genes differentially expressed after 48 h of fasting was 3.5-fold higher than after 16 h of fasting. Four clusters of co-expressed genes were identified by a hierarchical cluster analysis. Gene Ontology, KEGG and Ingenuity databases were then used to identify the metabolic processes associated to each cluster. After 16 h of fasting, genes involved in ketogenesis, gluconeogenesis and mitochondrial or peroxisomal fatty acid beta-oxidation, were up-regulated (cluster-1) whereas genes involved in fatty acid and cholesterol synthesis were down-regulated (cluster-2). For all genes tested, the microarray data was confirmed by quantitative RT-PCR. Most genes were altered by fasting as already reported in mammals. A notable exception was the HMG-CoA synthase 1 gene, which was up-regulated following 16 and 48 h of fasting while the other genes involved in cholesterol metabolism were down-regulated as reported in mammalian studies. We further focused on genes not represented on the microarray and candidates for the regulation of the target genes belonging to cluster-1 and -2 and involved in lipid metabolism. Data are provided concerning PPARa, SREBP1, SREBP2, NR1H3 transcription factors and two desaturases (FADS1, FADS2).

      Conclusion

      This study evidences numerous genes altered by starvation in chickens and suggests a global repression of cellular activity in response to this stressor. The central role of lipid and acetyl-CoA metabolisms and its regulation at transcriptional level are confirmed in chicken liver in response to short-term fasting. Interesting expression modulations were observed for NR1H3, FADS1 and FADS2 genes. Further studies are needed to precise their role in the complex regulatory network controlling lipid metabolism.

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      Most cited references 76

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      Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.

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        Linear models and empirical bayes methods for assessing differential expression in microarray experiments.

        The problem of identifying differentially expressed genes in designed microarray experiments is considered. Lonnstedt and Speed (2002) derived an expression for the posterior odds of differential expression in a replicated two-color experiment using a simple hierarchical parametric model. The purpose of this paper is to develop the hierarchical model of Lonnstedt and Speed (2002) into a practical approach for general microarray experiments with arbitrary numbers of treatments and RNA samples. The model is reset in the context of general linear models with arbitrary coefficients and contrasts of interest. The approach applies equally well to both single channel and two color microarray experiments. Consistent, closed form estimators are derived for the hyperparameters in the model. The estimators proposed have robust behavior even for small numbers of arrays and allow for incomplete data arising from spot filtering or spot quality weights. The posterior odds statistic is reformulated in terms of a moderated t-statistic in which posterior residual standard deviations are used in place of ordinary standard deviations. The empirical Bayes approach is equivalent to shrinkage of the estimated sample variances towards a pooled estimate, resulting in far more stable inference when the number of arrays is small. The use of moderated t-statistics has the advantage over the posterior odds that the number of hyperparameters which need to estimated is reduced; in particular, knowledge of the non-null prior for the fold changes are not required. The moderated t-statistic is shown to follow a t-distribution with augmented degrees of freedom. The moderated t inferential approach extends to accommodate tests of composite null hypotheses through the use of moderated F-statistics. The performance of the methods is demonstrated in a simulation study. Results are presented for two publicly available data sets.
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          From genomics to chemical genomics: new developments in KEGG

          The increasing amount of genomic and molecular information is the basis for understanding higher-order biological systems, such as the cell and the organism, and their interactions with the environment, as well as for medical, industrial and other practical applications. The KEGG resource () provides a reference knowledge base for linking genomes to biological systems, categorized as building blocks in the genomic space (KEGG GENES) and the chemical space (KEGG LIGAND), and wiring diagrams of interaction networks and reaction networks (KEGG PATHWAY). A fourth component, KEGG BRITE, has been formally added to the KEGG suite of databases. This reflects our attempt to computerize functional interpretations as part of the pathway reconstruction process based on the hierarchically structured knowledge about the genomic, chemical and network spaces. In accordance with the new chemical genomics initiatives, the scope of KEGG LIGAND has been significantly expanded to cover both endogenous and exogenous molecules. Specifically, RPAIR contains curated chemical structure transformation patterns extracted from known enzymatic reactions, which would enable analysis of genome-environment interactions, such as the prediction of new reactions and new enzyme genes that would degrade new environmental compounds. Additionally, drug information is now stored separately and linked to new KEGG DRUG structure maps.
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            Author and article information

            Affiliations
            [1 ]INRA, UMR 598, Génétique Animale, F-35000 Rennes, France
            [2 ]Agrocampus Ouest, UMR 598, Génétique Animale, F-35000 Rennes, France
            [3 ]INRA, UR83, Station de Recherches Avicoles, F-37380 Nouzilly, France
            [4 ]INRA, SIGENAE, F-35000 Rennes, France
            [5 ]INRA, SIGENAE, F-31000 Toulouse, France
            [6 ]Plateforme Transcriptome OUEST-genopole Rennes, F-35000 Rennes, France
            Contributors
            Journal
            BMC Genomics
            BMC Genomics
            BioMed Central
            1471-2164
            2008
            17 December 2008
            : 9
            : 611
            2628918
            1471-2164-9-611
            19091074
            10.1186/1471-2164-9-611
            Copyright © 2008 Désert et al; licensee BioMed Central Ltd.

            This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Categories
            Research Article

            Genetics

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