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

Yiheng Chen,Luis B Agellon

doi:10.3390/genes11080943

Abstract

Fatty acid-binding proteins (Fabps) make up a family of widely distributed cytoplasmic lipid-binding proteins. The small intestine contains three predominant Fabp species, Fabp1, Fabp2, and Fabp6. Our previous studies showed that Fabp2 and Fabp6 gene-disrupted mice exhibited sexually dimorphic phenotypes. In this study, we carried out a systematic comparative analysis of the small intestinal transcriptomes of 10 week-old wild-type (WT) and Fabp gene-disrupted male and female mice. We found that the small intestinal transcriptome of male and female mice showed key differences in the gene expression profiles that affect major biological processes. The deletion of specific Fabp genes induced unique and sex-specific changes in the gene expression program, although some differentially expressed genes in certain genotypes were common to both sexes. Functional annotation and interaction network analyses revealed that the number and type of affected pathways, as well as the sets of interacting nodes in each of the Fabp genotypes, are partitioned by sex. To our knowledge, this is the first time that sex differences were identified and categorized at the transcriptome level in mice lacking different intestinal Fabps. The distinctive transcriptome profiles of WT male and female small intestine may predetermine the nature of transcriptional reprogramming that manifests as sexually dimorphic responses to the ablation of intestinal Fabp genes.

Highlights

Fatty acid-binding proteins (Fabps) are highly abundant cytoplasmic proteins that are found in several mammalian tissues [1]
44of of13 number was reduced in the Fabp2–/– and Fabp2–/–;Fabp6–/– mice whereas the Fabp6 gene deletion
This number was reduced in the Fabp2–/– and Fabp2–/– ;Fabp6–/– mice whereas the Fabp6 gene deletion increased the number of sex-biased genes (Figure 1a), suggesting that the deletion of the Fabp2 gene increased the number of sex-biased genes (Figure 1a), suggesting that the deletion of the Fabp2 gene or or both Fabp2 and Fabp6 genes made the intestinal gene expression of males and females more similar, both Fabp2 and Fabp6 genes made the intestinal gene expression of males and females more similar, while the disruption of the Fabp6 gene increased the sexual dimorphism at the transcriptome level

Summary

Introduction

Fatty acid-binding proteins (Fabps) are highly abundant cytoplasmic proteins that are found in several mammalian tissues [1]. Fabp ( known as L-FABP) was first found in the liver [4] but is present throughout the small intestine with the highest abundance occurring in the proximal portion of the organ [8]. It can bind fatty acids with a preference for unsaturated long-chain fatty acids as well as an assortment of other hydrophobic molecules including bile acids and fibrates [9,10]. A T94A variant of the human FABP1 gene has been found to be associated with reduced body weight as well as altered glucose metabolic response to lipid challenge [16].

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