Bioinformatics for the NuGO proof of principle study: analysis of gene expression in muscle of ApoE3*Leiden mice on a high-fat diet using PathVisio

Abstract

Insulin resistance is a characteristic of type-2 diabetes and its development is associated with an increased fat consumption. Muscle is one of the tissues that becomes insulin resistant after high fat (HF) feeding. The aim of the present study is to identify processes involved in the development of HF-induced insulin resistance in muscle of ApOE3*Leiden mice by using microarrays. These mice are known to become insulin resistant on a HF diet. Differential gene expression was measured in muscle using the Affymetrix mouse plus 2.0 array. To get more insight in the processes, affected pathway analysis was performed with a new tool, PathVisio. PathVisio is a pathway editor customized with plug-ins (1) to visualize microarray data on pathways and (2) to perform statistical analysis to select pathways of interest. The present study demonstrated that with pathway analysis, using PathVisio, a large variety of processes can be investigated. The significantly regulated genes in muscle of ApOE3*Leiden mice after 12 weeks of HF feeding were involved in several biological pathways including fatty acid beta oxidation, fatty acid biosynthesis, insulin signaling, oxidative stress and inflammation.

Fig. 1

Gene expression data mapped on the Mus musculus fatty acid beta oxidation 1 pathway. Fold changes are represented as a gradient and visualized per genebox on the left. Yellow boxes indicate a significance of P ≤ 0.05 and are visualized per genebox on the right. Light gray boxes indicate not significant and are also visualized on the right. The dark gray boxes represent the genes that could not be measured

Fig. 2

Gene expression data mapped on the Mus musculus fatty acid synthesis pathway. Fold changes are represented as a gradient and visualized per genebox on the left. Yellow boxes indicate a significance of P ≤ 0.05 and are visualized per genebox on the right. Light gray boxes indicate not significant and are also visualized on the right. The dark gray boxes represent the genes that could not be measured

Fig. 3

Gene expression data mapped on the mouse insulin signaling pathway. Fold changes are represented as a gradient and visualized per genebox on the left. Yellow boxes indicate a significance of P ≤ 0.05 and are visualized per genebox on the right. Light gray boxes indicate not significant and are also visualized on the right. The dark gray boxes represent the genes that could not be measured