Common dysregulated pathways in obese adipose tissue and atherosclerosis

Abstract

BackgroundThe metabolic syndrome is becoming increasingly prevalent in the general population that is at simultaneous risk for both type 2 diabetes and cardiovascular disease. The critical pathogenic mechanisms underlying these diseases are obesity-driven insulin resistance and atherosclerosis, respectively. To obtain a better understanding of molecular mechanisms involved in pathogenesis of the metabolic syndrome as a basis for future treatment strategies, studies considering both inherent risks, namely metabolic and cardiovascular, are needed. Hence, the aim of this study was to identify pathways commonly dysregulated in obese adipose tissue and atherosclerotic plaques.MethodsWe carried out a gene set enrichment analysis utilizing data from two microarray experiments with obese white adipose tissue and atherosclerotic aortae as well as respective controls using a combined insulin resistance-atherosclerosis mouse model.ResultsWe identified 22 dysregulated pathways common to both tissues with p values below 0.05, and selected inflammatory response and oxidative phosphorylation pathways from the Hallmark gene set to conduct a deeper evaluation at the single gene level. This analysis provided evidence of a vast overlap in gene expression alterations in obese adipose tissue and atherosclerosis with Il7r, C3ar1, Tlr1, Rgs1 and Semad4d being the highest ranked genes for the inflammatory response pathway and Maob, Bckdha, Aldh6a1, Echs1 and Cox8a for the oxidative phosphorylation pathway.ConclusionsIn conclusion, this study provides extensive evidence for common pathogenic pathways underlying obesity-driven insulin resistance and atherogenesis which could provide a basis for the development of novel strategies to simultaneously prevent type 2 diabetes and cardiovascular disease in patients with metabolic syndrome.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0441-2) contains supplementary material, which is available to authorized users.

Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects

“…An applied approach is consistent with the work of other researchers, who investigated the skeletal muscle gene expression profile in MetS patients with the use of microarrays [22]. The analysis of pathway enrichment, in contrast to a single gene approach, yields the information on the network of biological interactions, allowing to detect changes at a higher biological level than individual genes or molecules, and thus contributing to a better understanding of the complexity of the disease [23]. It also seems a reasonable choice, when taking into account the limited statistical power of the study, resulting from low sample size, and the nature of investigated condition.…”

Brown adipose expansion and remission of glycemic dysfunction in obese SM/J mice

“…We highlight 8 cytokines and ECM genes that significantly change expression in a direction associated with improved metabolic health in previous studies. Il7r, which was found to be one of the highest ranking genes in the white adipose tissue inflammatory response pathway (40), decreases expression between 20 and 30 weeks of age in high fat-fed SM/J brown adipose. Col8a1 and Sema3C are both associated with adipose tissue fibrosis (17,41).…”

Smoking affects gene expression in blood of patients with ischemic stroke

“…IL7 regulates T‐cell differentiation, survival, and homeostasis, which mediates inflammation upon binding to IL7R . Increased gene expression of IL7R and lnc‐IL7R are observed in many inflammatory conditions including atherosclerotic plaques in humans . Thus, the dysregulation of some of the above T‐cell receptor signaling pathways could contribute to worsened ischemic brain injury in smokers.…”