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      Transcriptomic and metabolomic profiling of chicken adipose tissue in response to insulin neutralization and fasting

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          Abstract

          Background

          Domestic broiler chickens rapidly accumulate adipose tissue due to intensive genetic selection for rapid growth and are naturally hyperglycemic and insulin resistant, making them an attractive addition to the suite of rodent models used for studies of obesity and type 2 diabetes in humans. Furthermore, chicken adipose tissue is considered as poorly sensitive to insulin and lipolysis is under glucagon control. Excessive fat accumulation is also an economic and environmental concern for the broiler industry due to the loss of feed efficiency and excessive nitrogen wasting, as well as a negative trait for consumers who are increasingly conscious of dietary fat intake. Understanding the control of avian adipose tissue metabolism would both enhance the utility of chicken as a model organism for human obesity and insulin resistance and highlight new approaches to reduce fat deposition in commercial chickens.

          Results

          We combined transcriptomics and metabolomics to characterize the response of chicken adipose tissue to two energy manipulations, fasting and insulin deprivation in the fed state. Sixteen to 17 day-old commercial broiler chickens (ISA915) were fed ad libitum, fasted for five hours, or fed but deprived of insulin by injections of anti-insulin serum. Pair-wise contrasts of expression data identified a total of 2016 genes that were differentially expressed after correction for multiple testing, with the vast majority of differences due to fasting (1780 genes). Gene Ontology and KEGG pathway analyses indicated that a short term fast impacted expression of genes in a broad selection of pathways related to metabolism, signaling and adipogenesis. The effects of insulin neutralization largely overlapped with the response to fasting, but with more modest effects on adipose tissue metabolism. Tissue metabolomics indicated unique effects of insulin on amino acid metabolism.

          Conclusions

          Collectively, these data provide a foundation for further study into the molecular basis for adipose expansion in commercial poultry and identify potential pathways through which fat accretion may be attenuated in the future through genetic selection or management practices. They also highlight chicken as a useful model organism in which to study the dynamic relationship between food intake, metabolism, and adipose tissue biology.

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          Most cited references44

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          Peroxisome proliferator-activated receptor alpha target genes.

          Peroxisome proliferator-activated receptors (PPARs) are nuclear proteins that belong to the superfamily of nuclear hormone receptors. They mediate the effects of small lipophilic compounds such as long-chain fatty acids and their derivatives on transcription of genes commonly called PPAR target genes. Here we review the involvement of PPARalpha in peroxisomal and mitochondrial fatty acid oxidation, microsomal fatty acid hydroxylation, lipoprotein, bile and amino acid metabolism, glucose homeostasis, biotransformation, inflammation control, hepato-carcinogenesis and other pathways, through a detailed analysis of the different known or putative PPARalpha target genes.
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            Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs.

            The mitochondrial pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid (FA) synthesis. Knowledge of the mechanisms that regulate PDC activity is important, because PDC inactivation is crucial for glucose conservation when glucose is scarce, whereas adequate PDC activity is required to allow both ATP and FA production from glucose. The mechanisms that control mammalian PDC activity include its phosphorylation (inactivation) by a family of pyruvate dehydrogenase kinases (PDKs 1-4) and its dephosphorylation (activation, reactivation) by the pyruvate dehydrogenase phosphate phosphatases (PDPs 1 and 2). Isoform-specific differences in kinetic parameters, regulation, and phosphorylation site specificity of the PDKs introduce variations in the regulation of PDC activity in differing endocrine and metabolic states. In this review, we summarize recent significant advances in our knowledge of the mechanisms regulating PDC with emphasis on the PDKs, in particular PDK4, whose expression is linked with sustained changes in tissue lipid handling and which may represent an attractive target for pharmacological interventions aimed at modulating whole body glucose, lipid, and lactate homeostasis in disease states.
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              Quorum sensing controls biofilm formation in Vibrio cholerae through modulation of cyclic di-GMP levels and repression of vpsT.

              Two chemical signaling systems, quorum sensing (QS) and 3',5'-cyclic diguanylic acid (c-di-GMP), reciprocally control biofilm formation in Vibrio cholerae. QS is the process by which bacteria communicate via the secretion and detection of autoinducers, and in V. cholerae, QS represses biofilm formation. c-di-GMP is an intracellular second messenger that contains information regarding local environmental conditions, and in V. cholerae, c-di-GMP activates biofilm formation. Here we show that HapR, a major regulator of QS, represses biofilm formation in V. cholerae through two distinct mechanisms. HapR controls the transcription of 14 genes encoding a group of proteins that synthesize and degrade c-di-GMP. The net effect of this transcriptional program is a reduction in cellular c-di-GMP levels at high cell density and, consequently, a decrease in biofilm formation. Increasing the c-di-GMP concentration at high cell density to the level present in the low-cell-density QS state restores biofilm formation, showing that c-di-GMP is epistatic to QS in the control of biofilm formation in V. cholerae. In addition, HapR binds to and directly represses the expression of the biofilm transcriptional activator, vpsT. Together, our results suggest that V. cholerae integrates information about the vicinal bacterial community contained in extracellular QS autoinducers with the intracellular environmental information encoded in c-di-GMP to control biofilm formation.
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                Author and article information

                Contributors
                Journal
                BMC Genomics
                BMC Genomics
                BMC Genomics
                BioMed Central
                1471-2164
                2012
                31 August 2012
                : 13
                : 441
                Affiliations
                [1 ]Department of Animal Science, University of Tennessee, Knoxville, Tennessee, USA
                [2 ]Department of Chemistry, University of Tennessee, Knoxville, Tennessee, USA
                [3 ]Unité de Recherches Avicoles (U83), Institut National de la Recherche Agronomique (INRA), Nouzilly, 37380, France
                [4 ]Unité de Physiologie de la Reproduction et des Comportements (UMR85), Institut National de la Recherche Agronomique (INRA), Nouzilly, 37380, France
                [5 ]201E McCord Hall, Morgan Circle Dr. Knoxville, Tennessee, 2640, USA
                Article
                1471-2164-13-441
                10.1186/1471-2164-13-441
                3503602
                22938590
                b943bdae-2e8c-42ba-818c-655e915edaf7
                Copyright ©2012 Ji 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.

                History
                : 23 December 2011
                : 25 August 2012
                Categories
                Research Article

                Genetics
                chicken adipose tissue,insulin neutralization,fasting,glucose metabolism,microarray,fatty acid metabolism,adipogenesis

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