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Research Article

High Serum miR-421 is Associated with Metabolic Dysregulation and Inflammation in Patients with Metabolic Syndrome

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Pages 423-436 | Received 11 Jun 2020, Accepted 29 Jan 2021, Published online: 08 Mar 2021
 

Abstract

Aim: To explore the association of circulating miRNAs with adiposity, metabolic status and inflammatory biomarkers in patients with metabolic syndrome (MetS). Methods: Serum levels of 372 miRNAs were measured in patients with (n = 6) and without MetS (n = 6) by quantitative PCR array, and dysregulated miRNAs were validated in a larger cohort (MetS, n = 89; non-MetS, n = 144). Results: In the screening study, seven miRNAs were dysregulated in patients with MetS, and miR-421 remained increased in the validation study. miR-421 was associated with a high risk of MetS and insulin resistance and hypertension and correlated with glycated hemoglobin, triacylglycerols, high-sensitivity CRP, IL-6, resistin and adiponectin (p < 0.05). Conclusion: Circulating miR-421 is a potential biomarker for insulin resistance, metabolic dysregulation and inflammatory status in patients with MetS.

Lay abstract

This study aimed to explore the association of circulating regulatory small molecules (miRNAs) with obesity, metabolic alterations and inflammation in patients with metabolic syndrome (MetS). Levels of 372 miRNAs were measured in blood serum of patients with and without MetS using molecular biology techniques. Seven miRNAs were altered in patients with MetS, and one of them (miR-421) was associated with a high risk of MetS, insulin resistance and hypertension. miR-421 was also correlated with glycated hemoglobin (used for glycemia monitoring), serum lipids and inflammatory molecules. Circulating miR-421 is a small molecule with potential biomarker for insulin resistance, metabolic dysregulation and inflammatory status in patients with MetS.

Graphical abstract

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2020-0247

MH Hirata conceived and designed the research. R Curi and TC Pithon-Curi also contributed to the design of the research. AA Braga, LN Masi, MF Sampaio and LR de Castro collected samples and clinical data. AA Braga, ME Graciano-Saldarriaga, HT Lin-Wang and JB Borges performed the experiments. AA Braga, RH Bortolin, TDC Hirata, A Cerda, RCC de Freitas, JID França and GM Bastos analyzed and interpreted the data. RH Bortolin and AA Braga wrote the manuscript. RDC Hirata, MH Hirata, R Curi, TC TC Pithon-Curi and A Cerda performed the critical revision of the paper. All authors read and approved the final manuscript.

Acknowledgments

We thank A Garofalo for assisting in the patient recruitment process.

Financial & competing interests disclosure

This study was supported by grants from CNPq-Brazil (#457334/2013-4), CAPES-Brazil (# Code 001) and CONICYT-Chile (# REDI170632). AA Braga and ME Graciano-Saldarriaga were recipients of fellowships from CNPq, Brazil. MH Hirata, RDC Hirata and R Curi are recipients of fellowships from CNPq, Brazil. TDC Hirata and LN Masi were recipients of fellowships from FAPESP, Brazil. RH Bortolin and RCC de Freitas are recipients of fellowships from FAPESP, Brazil. A Cerda was a recipient of a fellowship from CONICYT, Chile. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript supported by grants from CNPq-Brazil (#457334/2013-4).

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported by grants from CNPq-Brazil (#457334/2013-4), CAPES-Brazil (# Code 001) and CONICYT-Chile (# REDI170632). AA Braga and ME Graciano-Saldarriaga were recipients of fellowships from CNPq, Brazil. MH Hirata, RDC Hirata and R Curi are recipients of fellowships from CNPq, Brazil. TDC Hirata and LN Masi were recipients of fellowships from FAPESP, Brazil. RH Bortolin and RCC de Freitas are recipients of fellowships from FAPESP, Brazil. A Cerda was a recipient of a fellowship from CONICYT, Chile. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was utilized in the production of this manuscript supported by grants from CNPq-Brazil (#457334/2013-4).

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