Abstract
BackgroundInsulin resistance (IR) in obesity is associated with the occurrence of metabolic and cardiovascular diseases. Dipepidyl peptidase 4 (DPP4) plays a pivotal role during the development of IR, and was found to be a target gene of microRNA-214 (miR-214) in our study. This study sought to assess the expression and clinical value of miR-214 in obese patients with IR, and investigate its therapeutic potential in obese rats and adipocytes with IR.MethodsSerum expression of miR-214 in obese patients with or without IR was estimated by quantitative real-time-PCR. A receiver operating characteristic curve was plotted to evaluate the diagnostic value of miR-214 in the patients. Obesity-induced IR animal and cell models were constructed, and the therapeutic ability of miR-214 was explored.ResultsSerum expression of miR-214 was decreased in obese patients compared with the healthy controls, and the lowest expression was observed in the cases with IR. Downregulation of miR-214 was significantly correlated with the serum DPP4 levels and HOMA-IR of the patients upon IR conditions, and was demonstrated to perform diagnostic accuracy for distinguishing obese patients with IR from those without IR. In obesity-associated IR animal and cell models, the downregulation of miR-214 was also been detected. According to the measurement of glucose and insulin tolerance and glucose uptake abilities, we found that the overexpression of miR-214 could be used to alleviate IR in the IR models, especially when collaboratively used with DPP4 inhibitor vildagliptin.ConclusionAll data revealed that miR-214, as a regulator of DPP4, is decreased in obese patients with IR and may serve as a diagnostic biomarker. The upregulation of miR-214 could improve IR in obese rats and adipocytes, indicating that miR-214 has the therapeutic potential for obesity and IR.
Highlights
Obesity becomes a major global health burden due to the comorbidities resulted from excessive adiposity, such as hyperglycemia, diabetes mellitus (DM) and insulin resistance (IR) [1]
Dipepidyl peptidase 4 (DPP4) is a direct target gene of miR-214 According to the bioinformatics analysis, we realized that DPP4 is a target gene of miR-214 with a complementary sequence of miR-214 in its 3′-UTR (Fig. 1a)
The expression of miR-214 in the adipocytes was regulated by miR-214 mimic and miR-214 inhibitor, which separately led to the upregulation and downregulation of miR-214
Summary
Obesity becomes a major global health burden due to the comorbidities resulted from excessive adiposity, such as hyperglycemia, diabetes mellitus (DM) and insulin resistance (IR) [1]. MicroRNAs (miRNAs) are a group of small noncoding RNAs with regulatory roles of gene expression at the post-transcriptional level [10]. They are involved in the pathogenesis of various human diseases, including obesity, by regulating the expression of key genes of the disease progression [4, 11]. It is noticeable that the regulatory function of miR-214 in inflammatory response has been demonstrated, and it is determined as one of the key molecules that serve as potential therapeutic targets in inflammation-associated diseases [17]. Dipepidyl peptidase 4 (DPP4) plays a pivotal role during the development of IR, and was found to be a target gene of microRNA-214 (miR-214) in our study. This study sought to assess the expression and clinical value of miR-214 in obese patients with IR, and investigate its therapeutic potential in obese rats and adipocytes with IR
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