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Analysis of Hepatic Gene Expression in Chickens with Hormonally-Induced Lean and Fat Phenotypes

ABSTRACT: Obesity is a growing health concern in the United States and has been linked to a global epidemic--the metabolic syndrome. The purpose of this project was to use microarray analysis to unravel the genetic circuits controlling deposition and metabolism of fat in a hormonally-induced obesity model. Glucose, triglyceride, and free fatty acid levels of four-week-old chickens were dramatically altered after acute infusion (six days) of exogenous corticosterone (CS), effectively producing a fat phenotype. A lean phenotype was induced by thyroid hormone (T3), and the interaction of both hormones (CS+T3) was also examined. The Del-Mar 14K Chicken Integrated Systems Microarray (Geo Platform GPL1731) was used to identify differentially expressed hepatic genes (false discovery rate, P < 0.05). In the contrast of fat (CS) and lean (T3) phenotypes, 231 genes were up-regulated by CS, whereas 532 genes were up-regulated by T3. This study revealed several transport proteins, transcription factors, and metabolic enzymes that control lipogenic (CS induced) and lipolytic (T3 induced) pathways. Also, the divergent expression of three genes belonging to the β-defensin family (DEFB9, DEFB10, and DEFB11) suggests a novel role for these antimicrobial peptides in adiposity. This project provides new insight into genetic control of metabolic disorders, such as diabetes and obesity. Keywords: Hormonal treatment on hepatic gene expression levels

ORGANISM(S): Gallus gallus

PROVIDER: GSE5205 | GEO | 2006/08/09

SECONDARY ACCESSION(S): PRJNA96493

REPOSITORIES: GEO

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Project description:Chickens divergently selected for either high abdominal fat content (fat genotype) or low abdominal fat content (lean genotype) at SRA-INRA, France were used to profile abdominal adipose gene expression during juvenile development (1 to 11 weeks of age) and to identify differentially expressed genes associated with genotype and age. The fat line (FL) and lean line (LL) chickens are different in various phenotypic and metabolic measurements, including abdominal fatness, plasma glycemia and T3. The FL and LL chickens represent unique models for characterizing biomedical and agricultural traits. The Del-Mar 14K Chicken Integrated Systems microarrays were used for a transcriptional scan in abdominal adipose during juvenile development using a balanced block hybridization design. Fluorescence intensities were normalized within array (without background subtraction), and between array (aquantile method) in LIMMA package R [Smyth, G. K. (2004) Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Statistical Applications in Genetics and Molecular Biology, Vol. 3, No. 1, Article 3] producing M-values (log-2 expression ratios) and A-values (average log-2 expression values). Normalized values were analyzed using a two factor ANOVA model. A total of 1,020 differentially expressed functional genes were identified (FDR<0.05). Genes were determined to have a significant effect of age (422), genotype (344), or an age by genotype interaction (254). The differentially expressed genes include metabolic enzymes, acute phase proteins, growth factors, coagulation factors, immune factors and transcription factors involved in various pathways. Several of the functional genes are also identified as positional candidate genes within QTLs in an F2 population established from an intercross between the FL and LL lines. Keywords: Divergently selected chickens, fatness, transcriptional profiling, differentially expressed genes A balanced block design was used for microarray hybridizations, where half of the birds of each genotype and age were labeled with Alexa Flour 647 (red) and the other half with Alexa Flour 555 (green). Four biological replicates were used for each genotype (FL or LL) at six different ages (1, 3, 5, 7, 9 and 11 wk).

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Analysis of Hepatic Gene Expression in Chickens with Hormonally-Induced Lean and Fat Phenotypes

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