Abstract
BackgroundWorldwide, the prevalence of obesity and insulin resistance has grown dramatically. Gene expression profiling in blood represents a powerful means to explore disease pathogenesis, but the potential impact of inter-individual differences in a cell-type profile is not always taken into account. The objective of this project was to investigate the whole blood transcriptome profile of insulin-resistant as compared to insulin-sensitive individuals independent of inter-individual differences in white blood cell profile.ResultsWe report a 3% higher relative amount of monocytes in the insulin-resistant individuals. Furthermore, independent of their white blood cell profile, insulin-resistant participants had (i) higher expression of interferon-stimulated genes and (ii) lower expression of genes involved in cellular differentiation and remodeling of the actin cytoskeleton.ConclusionsWe present an approach to investigate the whole blood transcriptome of insulin-resistant individuals, independent of their DNA methylation-derived white blood cell profile. An interferon-related signature characterizes the whole blood transcriptome profile of the insulin-resistant individuals, independent of their white blood cell profile. The observed signature indicates increased systemic inflammation possibly due to an innate immune response and whole-body insulin resistance, which can be a cause or a consequence of insulin resistance. Altered gene expression in specific organs may be reflected in whole blood; hence, our results may reflect obesity and/or insulin resistance-related organ dysfunction in the insulin-resistant individuals.
Highlights
IntroductionGene expression profiling in blood represents a powerful means to explore disease pathogenesis, but the potential impact of interindividual differences in a cell-type profile is not always taken into account
Worldwide, the prevalence of obesity and insulin resistance has grown dramatically
Studies performed in human and mouse have shown that accumulation of T cells precedes macrophage accumulation in obese adipose tissue [3] and that numerous changes in their subpopulations are linked to the development of obesity and insulin resistance in animal models [4]
Summary
Gene expression profiling in blood represents a powerful means to explore disease pathogenesis, but the potential impact of interindividual differences in a cell-type profile is not always taken into account The objective of this project was to investigate the whole blood transcriptome profile of insulin-resistant as compared to insulin-sensitive individuals independent of inter-individual differences in white blood cell profile. Differential gene expression analysis performed in the blood does not always take into account the potential impact from the inter-individual differences in a cell-type profile. These differences might represent changes on the cell type-specific level and reflect changes in biologically relevant tissues
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