Visualization of Sex-Dimorphic Changes in the Intestinal Transcriptome of Fabp2 Gene-Ablated Mice
Background/Aims: Sex differences in gene expression program have not been effectively explored at the transcriptome level. We aimed to develop a method for the analysis of transcriptome data to identify sex differences and sex-dimorphic responses to experimental conditions in mice. Methods: Profilin...
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| Published in | Journal of nutrigenetics and nutrigenomics Vol. 5; no. 1; pp. 45 - 55 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Basel, Switzerland
01.01.2012
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2504-3161 2504-3188 1661-6758 |
| DOI | 10.1159/000337193 |
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| Abstract | Background/Aims: Sex differences in gene expression program have not been effectively explored at the transcriptome level. We aimed to develop a method for the analysis of transcriptome data to identify sex differences and sex-dimorphic responses to experimental conditions in mice. Methods: Profiling of the small intestine transcriptome of chow-fed C57BL/6J (wild-type, WT) and Fabp2 –/– mice was carried out by microarray analysis. Sex-specific and androgynous effects of Fabp2 gene ablation were examined using FlexArray V1.6 by comparing WT to Fabp2 –/– mice. The data generated were exported into a single spreadsheet, collated and transformed to identify the differentially expressed genes for pathway analysis. Results: The method revealed enrichment of 17 sex-dimorphic pathways in the small intestine of WT mice compared to only 4 in Fabp2 –/– mice. Comparison of the effects of Fabp2 loss in individual sexes revealed a male-specific upregulation of 5 pathways involved in the production of unsaturated fatty acids, and a female-specific downregulation of pathways involved in xenobiotic metabolism. Conclusions: Our approach detected the common as well as sex-differential pathways that are modified due to the loss of Fabp2. These findings suggest that the pathways involved in nutrient and xenobiotic metabolism in the intestine are regulated by sex-specific mechanisms. |
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| AbstractList | Background/Aims: Sex differences in gene expression program have not been effectively explored at the transcriptome level. We aimed to develop a method for the analysis of transcriptome data to identify sex differences and sex-dimorphic responses to experimental conditions in mice. Methods: Profiling of the small intestine transcriptome of chow-fed C57BL/6J (wild-type, WT) and Fabp2–/– mice was carried out by microarray analysis. Sex-specific and androgynous effects of Fabp2 gene ablation were examined using FlexArray V1.6 by comparing WT to Fabp2–/– mice. The data generated were exported into a single spreadsheet, collated and transformed to identify the differentially expressed genes for pathway analysis. Results: The method revealed enrichment of 17 sex-dimorphic pathways in the small intestine of WT mice compared to only 4 in Fabp2–/– mice. Comparison of the effects of Fabp2 loss in individual sexes revealed a male-specific upregulation of 5 pathways involved in the production of unsaturated fatty acids, and a female-specific downregulation of pathways involved in xenobiotic metabolism. Conclusions: Our approach detected the common as well as sex-differential pathways that are modified due to the loss of Fabp2. These findings suggest that the pathways involved in nutrient and xenobiotic metabolism in the intestine are regulated by sex-specific mechanisms. Sex differences in gene expression program have not been effectively explored at the transcriptome level. We aimed to develop a method for the analysis of transcriptome data to identify sex differences and sex-dimorphic responses to experimental conditions in mice. Profiling of the small intestine transcriptome of chow-fed C57BL/6J (wild-type, WT) and Fabp2⁻/⁻ mice was carried out by microarray analysis. Sex-specific and androgynous effects of Fabp2 gene ablation were examined using FlexArray V1.6 by comparing WT to Fabp2⁻/⁻ mice. The data generated were exported into a single spreadsheet, collated and transformed to identify the differentially expressed genes for pathway analysis. The method revealed enrichment of 17 sex-dimorphic pathways in the small intestine of WT mice compared to only 4 in Fabp2⁻/⁻ mice. Comparison of the effects of Fabp2 loss in individual sexes revealed a male-specific upregulation of 5 pathways involved in the production of unsaturated fatty acids, and a female-specific downregulation of pathways involved in xenobiotic metabolism. Our approach detected the common as well as sex-differential pathways that are modified due to the loss of Fabp2. These findings suggest that the pathways involved in nutrient and xenobiotic metabolism in the intestine are regulated by sex-specific mechanisms. |
| Author | Agellon, Luis B. Agellon, Al B. Sugiyama, Michael G. Hobson, Luc |
| Author_xml | – sequence: 1 givenname: Michael G. surname: Sugiyama fullname: Sugiyama, Michael G. – sequence: 2 givenname: Luc surname: Hobson fullname: Hobson, Luc – sequence: 3 givenname: Al B. surname: Agellon fullname: Agellon, Al B. email: luis.agellon@mcgill.ca – sequence: 4 givenname: Luis B. surname: Agellon fullname: Agellon, Luis B. email: luis.agellon@mcgill.ca |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22584290$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.2337%2Fdiabetes.50.1.69 10.1517%2F17425255.4.4.413 10.1038%2Foby.2007.171 10.1055%2Fs-2006-925405 10.1093%2Fbiostatistics%2F4.2.249 10.1093%2Fnar%2Fgkp896 10.1084%2Fjem.20061839 10.1124%2Fdmd.107.019349 10.1172%2FJCI117778 10.1016%2Fj.metabol.2006.11.014 10.1139%2Fo11-067 10.1093%2Fhmg%2Fddh240 10.1023%2FA%3A1020520521025 10.1038%2Fnm1185 10.1016%2FS0014-5793%2803%2900578-7 10.1073%2Fpnas.091062498 10.1007%2Fs00125-003-1289-z 10.1096%2Ffj.99-0959com 10.1007%2Fs11010-005-9042-1 10.1093%2Fnar%2Fgki475 10.1152%2Fphysiolgenomics.00198.2006 10.1016%2FS0092-8674%2801%2980012-X 10.1152%2Fajpgi.00229.2010 10.1172%2FJCI118285 10.1210%2Fen.2002-220630 10.1248%2Fbpb.30.818 10.1152%2Fphysiolgenomics.00110.2009 10.1021%2Fbi000314z 10.1111%2Fj.1749-6632.2002.tb04315.x 10.1006%2Fabio.1987.9999 10.1172%2FJCI26498 |
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| Copyright | 2012 S. Karger AG, Basel Copyright © 2012 S. Karger AG, Basel. |
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| Keywords | Transcriptome analysis Fatty acid binding proteins Sex differences Lipid metabolism Method Small intestine KEGG pathways |
| Language | English |
| License | Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. https://www.karger.com/Services/SiteLicenses Copyright © 2012 S. Karger AG, Basel. |
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| PublicationTitle | Journal of nutrigenetics and nutrigenomics |
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| References_xml | – reference: Agellon LB, Li L, Luong L, Uwiera RR: Adaptations to the loss of intestinal fatty acid binding protein in mice. Mol Cell Biochem 2006;284:159–166.10.1007%2Fs11010-005-9042-1 – reference: Lofgren S, Baldwin RM, Hiratsuka M, Lindqvist A, Carlberg A, Sim SC, Schulke M, Snait M, Edenro A, Fransson-Steen R, Terelius Y, Ingelman-Sundberg M: Generation of mice transgenic for human CYP2C18 and CYP2C19: characterization of the sexually dimorphic gene and enzyme expression. Drug Metab Dispos 2008;36:955–962.10.1124%2Fdmd.107.019349 – reference: Tai ES, bin Ali A, Zhang Q, Loh LM, Tan CE, Retnam L, El Oakley RM, Lim SK: Hepatic expression of PPARalpha, a molecular target of fibrates, is regulated during inflammation in a gender-specific manner. FEBS Lett 2003;546:237–240.10.1016%2FS0014-5793%2803%2900578-7 – reference: Kadowaki K, Fukino K, Negishi E, Ueno K: Sex differences in PPARgamma expressions in rat adipose tissues. Biol Pharm Bull 2007;30:818–820.10.1248%2Fbpb.30.818 – reference: Ditton HJ, Zimmer J, Kamp C, Rajpert-De Meyts E, Vogt PH: The AZFa gene DBY (DDX3Y) is widely transcribed but the protein is limited to the male germ cells by translation control. Hum Mol Genet 2004;13:2333–2341.1529487610.1093%2Fhmg%2Fddh240 – reference: Geschonke K, Klempt M, Lynch N, Schreiber S, Fenselau S, Schrezenmeir J: Detection of a promoter polymorphism in the gene of intestinal fatty acid binding protein (I-FABP). Ann N Y Acad Sci 2002;967:548–553.10.1111%2Fj.1749-6632.2002.tb04315.x – reference: Formanack ML, Baier LJ: Variation in the FABP2 promoter affects gene expression: implications for prior association studies. Diabetologia 2004;47:349–351.10.1007%2Fs00125-003-1289-z – reference: Yoon M, Jeong S, Nicol CJ, Lee H, Han M, Kim JJ, Seo YJ, Ryu C, Oh GT: Fenofibrate regulates obesity and lipid metabolism with sexual dimorphism. Exp Mol Med 2002;34:481–488. – reference: Chomczynski P, Sacchi N: Single-step method of rna isolation by acid guanidinium thiocyanate phenol chloroform extraction. Analytical Biochemistry 1987;162:156–159.244033910.1006%2Fabio.1987.9999 – reference: Jensen MD: Gender differences in regional fatty acid metabolism before and after meal ingestion. J Clin Invest 1995;96:2297–2303.10.1172%2FJCI118285 – reference: Helwig U, Rubin D, Klapper M, Li Y, Nothnagel M, Folsch UR, Doring F, Schreiber S, Schrezenmeir J: The association of fatty acid-binding protein 2 A54T polymorphism with postprandial lipemia depends on promoter variability. Metabolism 2007;56:723–731.10.1016%2Fj.metabol.2006.11.014 – reference: Agellon LB, Drozdowski L, Li L, Iordache C, Luong L, Clandinin MT, Uwiera RR, Toth MJ, Thomson AB: Loss of intestinal fatty acid binding protein increases the susceptibility of male mice to high fat diet-induced fatty liver. Biochim Biophys Acta 2007;1771:1283–1288. – reference: Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M: MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 2006;116:1494–1505.1669129110.1172%2FJCI26498 – reference: Agellon LB, Toth MJ, Thomson AB: Intracellular lipid binding proteins of the small intestine. Mol Cell Biochem 2002;239:79–82.10.1023%2FA%3A1020520521025 – reference: Bunger M, van den Bosch HM, van der Meijde J, Kersten S, Hooiveld GJ, Muller M: Genome-wide analysis of PPARalpha activation in murine small intestine. Physiol Genomics 2007;30:192–204.10.1152%2Fphysiolgenomics.00198.2006 – reference: Sakuma T, Masaki K, Itoh S, Yokoi T, Kamataki T: Sex-related differences in the expression of cytochrome P450 in hamsters: cDNA cloning and examination of the expression of three distinct CYP2C cDNAs. 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| Snippet | Background/Aims: Sex differences in gene expression program have not been effectively explored at the transcriptome level. We aimed to develop a method for the... Sex differences in gene expression program have not been effectively explored at the transcriptome level. We aimed to develop a method for the analysis of... |
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| SubjectTerms | Animals Down-Regulation Fatty Acid-Binding Proteins - genetics Female Intestines - metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Original Paper Sex Characteristics Transcriptome Up-Regulation |
| Title | Visualization of Sex-Dimorphic Changes in the Intestinal Transcriptome of Fabp2 Gene-Ablated Mice |
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