Transcriptome analysis of the adipose tissue in a mouse model of metabolic syndrome identifies gene signatures related to disease pathogenesis

Highlights

• We performed microarray analysis of WAT in a mouse model of diet-induced MetS followed by in-depth bioinformatics analysis

• An increasing number of differentially expressed transcripts during MetS development was identified

• Most significant pathways were related to glucose and lipid metabolism, innate or adaptive immunity and tissue remodeling

• Upstream regulator analysis identified cytokine genes such as TGFβ and TNFα

• Microarray data were validated with RT-qPCR for representative genes of the various categories

• MasigPro analysis identified gene Clusters that could be exploited further as biomarkers or as novel therapeutic targets

Abstract

The white adipose tissue (WAT) contributes to the metabolic imbalance observed in obesity and the metabolic syndrome (MetS) by mechanisms that are poorly understood. The aim of this study was to monitor changes in the transcriptome of epididymal WAT during the development of MetS. ApoE3L.CETP mice were fed a high fat (HFD) or a low-fat (LFD) diet for different time periods. Adipose RNA was analyzed by microarrays. We found an increasing number of differentially expressed transcripts during MetS development. In mice with MetS, 1396 transcripts were differentially expressed including transcripts related to immune/inflammatory responses and extracellular matrix enzymes, suggesting significant inflammation and tissue remodeling. The top list of pathways included focal adhesion, chemokine, B and T cell receptor and MAPK signaling. The data identify for the first time adipose gene signatures in apoE3L.CETP mice with diet-induced MetS and might open new avenues for investigation of potential biomarkers or therapeutic targets.