Downregulation of Exosomal hsa-miR-551b-3p in Obesity and Its Link to Type 2 Diabetes Mellitus

Abstract

Obesity is a significant risk factor for the development of type 2 diabetes mellitus (T2DM). Adipose tissue dysfunction can affect the pool of circulating exosomal miRNAs, driving concomitant disease in obesity. These exosomal miRNAs can reflect adipose tissue functionality, thus serving as prognostic biomarkers for disease monitoring in case of T2DM. In the present study, we conducted NanoString microRNA profiling of extracellular vesicles (EVs) secreted by adipose tissue of obese patients (body mass index (BMI) > 35) without T2DM and nonobese individuals (BMI < 30) as a control group. Functional and pathway enrichment analysis showed that miRNAs associated with obesity in this study were implicated in insulin signaling and insulin resistance biological pathways. Further, these microRNAs were screened in serum EVs in the following groups: (1) obese patients with T2DM, (2) obese patients without T2DM, and (3) nonobese individuals as a control group. has-miR-551b-3p was shown to be downregulated in adipose tissue EVs, as well as in serum EVs, of patients with obesity without T2DM. At the same time, the serum exosomal hsa-miR-551b-3p content was significantly higher in obese patients with T2DM when compared with obese patients without T2DM and may be a potential biomarker of T2DM development in obesity.

Extracellular Vesicles Secreted by Adipose Tissue during Obesity and Type 2 Diabetes Mellitus Influence Reverse Cholesterol Transport-Related Gene Expression in Human Macrophages

“…This led to the hypothesis that adipocyte-derived EV microRNAs would target mRNAs involved in macrophage cholesterol efflux and that EVs, in part, exert their pro-atherogenic effect through the transfer of these microRNAs [16]. Obesity-driven changes in AT derived EV microRNAs were previously demonstrated by us and others and could be more dramatic in T2DM [15,27,28]. However, the definite miRNA content of AT EVs in T2DM remains unclear.…”

“…At the same time, AT EVs are important for the transport of adipokines: for example, 2–10% of adiponectin in serum is associated with EVs [ 29 ]. Adiponectin has been reported to upregulate an expression of the ABCA1 gene in human macrophages and enhance cholesterol efflux [ 15 , 30 ]. Lipids including cholesterol are also transported by AT EVs.…”

“…Recently, we described morphological changes in AT EVs during obesity [ 13 ]. Additionally, we and others showed that AT EV miRNA composition may also differ in obese patients and potentially could result in the dysregulation of gene expression linked to insulin resistance and lipid accumulation [ 15 , 16 ].…”

Epigenetic modifications in obesity‐associated diseases

“…AT serves as the primary origin of serum exosomes that can serve as indicators of AT function and potential prognostic markers for T2D. In obese patients with T2D, there is an elevation in hsa‐miR‐551b‐3p levels in both VAT and serum exosomes compared with obese patients without T2D, suggesting a potential association between miRNAs secretion and obesity‐induced lipid remodeling 172 . Furthermore, miR‐27‐3p overexpression in exosomes originating from M1 macrophages results in impaired mitochondrial autophagy through the suppression of ras homolog family member T1 (Rhot1) gene, which encodes mitochondrial rho GTPase 1 173 .…”

Adipose exosomal noncoding RNAs: Roles and mechanisms in metabolic diseases

“…Besides, the level of serum exosomal miR-551b-3p was significantly higher in patients with obesity and T2DM when compared with patients with obesity but without T2DM, which may be a potential biomarker of T2DM development in obesity. 132 In addition, there are other ncRNAs mentioned in section 4, whose levels were altered in the development of metabolic diseases, such as miR-378 and miR-222, which could also be promised biomarkers for diagnosis and treatment.…”