Visualization of Sex-Dimorphic Changes in the Intestinal Transcriptome of <b><i>Fabp2</i></b> Gene-Ablated Mice

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.

Direct Comparison of Mice Null for Liver or Intestinal Fatty Acid-binding Proteins Reveals Highly Divergent Phenotypic Responses to High Fat Feeding

“…On a high safflower oil diet that was fed for 2 weeks, older (30 -40 week) male and female IFABP Ϫ/Ϫ mice both gained more weight than WT mice, whereas on a high beef tallow diet, the males were found to have slightly (9%) higher body weights, with female IFABP Ϫ/Ϫ mice of the same age and on the same diet showing no body weight change (23). In addition to body weight differences, the relative absence of gene expression changes found by quantitative PCR analysis of mucosal samples for male IFABP Ϫ/Ϫ mice in this study is in contrast with results of a microarray analysis of intestinal RNA of male IFABP Ϫ/Ϫ mice from the original line, which showed significant differences compared with WT males, including increased expression of genes involved in fatty acid metabolism (63).…”

Distinct Alteration of Gene Expression Programs in the Small Intestine of Male and Female Mice in Response to Ablation of Intestinal Fabp Genes

“…Specifically, DE genes influenced by Fabp2 or Fabp6 gene single deletions are involved in metabolism-related biological processes, whereas combined Fabp2 and Fabp6 gene deletions mainly influenced immune-related biological processes. Furthermore, the males and females displayed distinct alterations of biological processes in response to the same Fabp gene ablation, which is concordant with previously reported changes observed in Fabp2 gene-disrupted mice [ 46 ].…”

Sex differences in the brain: a whole body perspective

“…Gene expression in the small intestine and colon differs in male and female mice and does so even before weaning [ 118 , 119 ]. In addition, adult males and females housed in the same environment and eating the same food exhibit differences in the gut microbiota (the collection of microorganisms living symbiotically in our intestines) [ 120 ].…”