Visceral Adipose Tissue of Prediabetic and Diabetic Females Shares a Set of Similarly Upregulated microRNAs Functionally Annotated to Inflammation, Oxidative Stress and Insulin Signaling

Abstract

Hypertrophic and hypoxic visceral adipose tissue (VAT) secretes proinflammatory cytokines promoting insulin resistance (IR), prediabetes and type 2 diabetes (T2DM) microRNAs (miRNAs) are markers of metabolic disorders regulating genes critical for e.g., inflammation, glucose metabolism, and antioxidant defense, with raising diagnostic value. The aim of the current study was to evaluate whether hyperglycemia is able to affect the expression of selected miRNAs in VAT of prediabetic (IFG) and diabetic (T2DM) patients vs. normoglycemic (NG) subjects using qPCR. Statistical analyses suggested that miRNAs expression could be sex-dependent. Thus, we determined 15 miRNAs as differentially expressed (DE) among NG, T2DM, IFG females (miR-10a-5p, let-7d-5p, miR-532-5p, miR-127-3p, miR-125b-5p, let-7a-5p, let-7e-5p, miR-199a-3p, miR-365a-3p, miR-99a-5p, miR-100-5p, miR-342-3p, miR-146b-5p, miR-204-5p, miR-409-3p). Majority of significantly changed miRNAs was similarly upregulated in VAT of female T2DM and IFG patients in comparison to NG subjects, positively correlated with FPG and HbA1c, yet, uncorrelated with WHR/BMI. Enrichment analyses indicated involvement of 11 top DE miRNAs in oxidative stress, inflammation and insulin signaling. Those miRNAs expression changes could be possibly associated with low-grade chronic inflammation and oxidative stress in VAT of hyperglycemic subjects.

Chronic and Intermittent Hyperglycemia Modulates Expression of Key Molecules of PI3K/AKT Pathway in Differentiating Human Visceral Adipocytes

“…Further, the effect seems to be postponed in time (alterations are significant mostly one stage after introducing HG). Overall, our data are in accordance with findings reported by Andersen et al [ 16 ] and partially support our earlier findings [ 5 , 7 , 60 ] that visceral Ads exhibit signs of metabolic memory. Obtained results suggest that miR-143-3p, miR-374-5p, and miR-152-3p may take part in preserving toxic effects of HG in Ads, however, the expression only of miR-152-3p may be related to genes analyzed in our study.…”

Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control

“…miR-342-3p promotes the adipogenesis in mesenchymal stem cells by suppressing CtBP2 and releasing C/EBPα from CtBP2 binding ( 22 ). In the female patients with T2D and impaired fasting glucose (IFG), miRNAs including miR-342-3p were upregulated and in silico enrichment analyses suggested the 11 top differentially expressed miRNAs possibly involved in oxidative stress, inflammation and insulin signaling ( 23 ). In our study, miR-342-3p was prominently expressed in SVF of epididymal adipose tissue and we were interested in the status of inflammation.…”

MicroRNA-204-5p reduction in rat hippocampus contributes to stress-induced pathology via targeting RGS12 signaling pathway

“…Based on KEEG analysis of miR-204-5p and its downstream predictive target genes and previous literature reports, it is concluded that miR-204-5p is associated with a variety of diseases related to the central nervous system [ 26 ]. Findings from previous reports revealed that miR-204-5p is involved in multiple signaling pathways and results from related studies have shown that miR-204-5p is involved with oxidative stress-related pathways, in specific to the oxidative capacity of mitochondria as demonstrated in vivo [ 27 – 29 ]. Accordingly, the potential role of miR-204-5p in depression became the focus of our research in this report.…”