Abstract
BackgroundInflammatory response plays a key role in the development of insulin resistance (IR) in obesity. Oxidative stress triggers the replication of the mitochondrial genome and division of the organelle. The purpose of this study was to identify the relationship of chemerin and TNF-α with mitochondrial DNA (mtDNA) copy number in subcutaneous adipose tissue (SAT) and visceral adipose tissue (mesentery of the small intestine (Mes), greater omentum (GO) and blood mononuclear cells (MNCs)) in patients with obesity with/without type 2 diabetes mellitus (T2DM).MethodsThe study included 142 obese patients and 34 healthy donors. The samples used for the study were peripheral venous blood (MNCs) and ATs (SAT, Mes and GO). The measurement of mtDNA copy number was done by droplet digital PCR. Quantitative determination of insulin, adiponectin, TNF-α and chemerin in serum/plasma was performed by flow-through fluorometry and commercial ELISA kit. Statistical analysis and graphs were obtained in R Statistical Software (version 3.3.1).ResultsThe increase in body mass index (BMI) was accompanied by an increase in TNF-α production, an increase in mtDNA copy number in SAT and a decrease in mtDNA copy number in MNCs. The negative association between plasma chemerin and mtDNA copy number in the Mes, as well as between mtDNA copy number and chemerin expression in the Mes, in the group with BMI > 40 kg/m2 without T2DM demonstrates the protective effect of chemerin against the development of IR via the regulation of mtDNA copy number in adipose tissues.ConclusionsWe thus speculated the existence of a compensatory mechanism in which leads to the increased number of mtDNA copies under the influence of proinflammatory factors. Based on the obtained data, we propose that reducing mtDNA copy number in cases of morbid obesity without T2DM has a positive effect on carbohydrate metabolism, which may help maintain glucose levels within reference values.Obesity, type 2 diabetes, mtDNA, cytokines, TNF-a, chemerin.
Highlights
Inflammatory response plays a key role in the development of insulin resistance (IR) in obesity
Plasma level of components of carbohydrate metabolism, proinflammatory mediators (TNF-α and CRP) and adipokines The level of glucose and the HOMA-IR was higher in obese patients with type 2 diabetes mellitus (T2DM) than in patients without T2DM and control individuals (p < 0.05) (Table 3)
With respect to the homeostasis of glucose, we have demonstrated the dual role of chemerin in obesity: positive - with obesity and no disruptions in carbohydrate metabolism and negative - with obesity associated with T2DM
Summary
Inflammatory response plays a key role in the development of insulin resistance (IR) in obesity [1, 2]. The malfunctioning of mitochondria leads to an energy crisis in insulin-dependent tissues and forms the foundation for the formation of IR [4, 5]. The high content of free fatty acids induces mitochondrial DNA (mtDNA) damage and causes the production of endoplasmic reticulum stress markers, protein degradation and apoptosis, contributing to increased oxidative stress in skeletal muscle cells and adipose tissues (ATs) [6]. Oxidative stress triggers the replication of the mitochondrial genome and division of the organelle [7, 8]
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