Abstract
BackgroundInsulin resistance (IR) is accompanied by chronic low grade systemic inflammation, obesity, and deregulation of total body energy homeostasis. We induced inflammation in adipose and liver tissues in vitro in order to mimic inflammation in vivo with the aim to identify tissue-specific processes implicated in IR and to find biomarkers indicative for tissue-specific IR.MethodsHuman adipose and liver tissues were cultured in the absence or presence of LPS and DNA Microarray Technology was applied for their transcriptome analysis. Gene Ontology (GO), gene functional analysis, and prediction of genes encoding for secretome were performed using publicly available bioinformatics tools (DAVID, STRING, SecretomeP). The transcriptome data were validated by proteomics analysis of the inflamed adipose tissue secretome.ResultsLPS treatment significantly affected 667 and 483 genes in adipose and liver tissues respectively. The GO analysis revealed that during inflammation adipose tissue, compared to liver tissue, had more significantly upregulated genes, GO terms, and functional clusters related to inflammation and angiogenesis. The secretome prediction led to identification of 399 and 236 genes in adipose and liver tissue respectively. The secretomes of both tissues shared 66 genes and the remaining genes were the differential candidate biomarkers indicative for inflamed adipose or liver tissue. The transcriptome data of the inflamed adipose tissue secretome showed excellent correlation with the proteomics data.ConclusionsThe higher number of altered proinflammatory genes, GO processes, and genes encoding for secretome during inflammation in adipose tissue compared to liver tissue, suggests that adipose tissue is the major organ contributing to the development of systemic inflammation observed in IR. The identified tissue-specific functional clusters and biomarkers might be used in a strategy for the development of tissue-targeted treatment of insulin resistance in patients.
Highlights
Insulin resistance (IR) is accompanied by chronic low grade systemic inflammation, obesity, and deregulation of total body energy homeostasis
The significantly changed genes found in adipose tissue and liver tissue which were not present on both platforms were discarded from further analysis (47 and 42 respectively)
The identified gene functional clusters such as: chemokine signaling, matrix remodelling, suppression of cytokine signaling (SOCS) signaling, PPARg and others are depicted in Figures 1, 2, 3, 4, and 5: the gene functional clusters identified for the significant, overlapping adipose and liver tissue transcriptomes (Figure 1), the significant, upregulated adipose tissue transcriptome (Figure 2), for the significant, downregulated adipose tissue transcriptome (Figure 3), the significant, upregulated liver tissue transcriptome (Figure 4), and the significant, downregulated liver tissue transcriptome (Figure 5)
Summary
Insulin resistance (IR) is accompanied by chronic low grade systemic inflammation, obesity, and deregulation of total body energy homeostasis. During the development of obesity, adipose tissue undergoes a switch from being mainly a metabolic organ towards an organ that shows substantial pro-inflammatory activity, associated with decreased insulin sensitivity, declined expression of adiponectin and enhanced production of pro-inflammatory cytokines and chemokines. These processes are believed to lead to low-grade inflammation and eventually systemic insulin resistance (IR) and type 2 diabetes (T2D) [2]. It is not yet understood how the change in the inflamed adipose tissue transcriptome and secretome leads to the development of IR. Except for the few proteins known to be produced and secreted by the liver during inflammation little is known about other protein factors which alone or by interacting with the secretome of inflamed adipose tissue could contribute to the development of systemic inflammation and insulin resistance in humans [5,6,7,8]
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