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Circulatory miRNA biomarkers of metabolic syndrome

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Abstract

Aims

Circulatory microRNAs (c-miRNAs) exert important roles in the molecular dysregulation of cardio-metabolic diseases. However, little is known whether dysregulated miRNA expression occurs when risk factors are elevated, as in the metabolic syndrome (MetS). This study quantified c-miRNA expression in individuals with MetS compared to healthy, further examining the relationship of gene pathways with the underlying pathogenesis.

Methods

Expression of 26 miRNAs was quantified in plasma from 40 women (20 healthy and 20 MetS) and 39 men (20 healthy and 19 MetS) by qPCR. In silico analysis was performed to investigate biological effects of the dysregulated miRNAs. Dysregulated miRNA expression was further validated in an independent cohort of 20 women (10 healthy and 10 MetS).

Results

Regression model adjusted for age and sex identified miR-15a-5p, miR-17-5p, miR-370-3p and miR-375 as important predictors of MetS presence. Analysis of predictive miRNAs in the validation cohort strengthened the relationship with miR-15a-5p and miR-17-5p expression. These miRNAs share genes involved in the regulation of metabolic pathways including insulin, wnt, fatty acid metabolism and AMPK.

Conclusions

miR-15a-5p and miR-17-5p were identified as predictive biomarkers of MetS, irrespective of sexes, further demonstrating the relationship of c-miRNAs to known pathways of metabolic disturbances present in cardio-metabolic diseases.

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Acknowledgements

The authors would like to acknowledge all the participants involved in this study.

Funding

This study was supported by AgResearch Limited through the Strategic Science Investment Fund (Nutritional strategies for an aging population, Contracts A19079 and A21246).

Author information

Authors and Affiliations

  1. Liggins Institute, The University of Auckland, 85 Park Road, Grafton, Private Bag 92019, Auckland, 1142, New Zealand

    F. Ramzan, R. F. D’Souza, B. R. Durainayagam, A. M. Milan, J. F. Markworth, C. J. Mitchell & D. Cameron-Smith

  2. Department of Statistics, The University of Auckland, Auckland, New Zealand

    V. Miranda-Soberanis

  3. Food Nutrition and Health Team, AgResearch Grasslands, Palmerston North, New Zealand

    N. C. Roy

  4. The Riddet Institute, Massey University, Palmerston North, New Zealand

    F. Ramzan, N. C. Roy, S. D. Poppitt & D. Cameron-Smith

  5. The High-Value Nutrition National Science Challenge, Auckland, New Zealand

    I. R. Sequeira, N. C. Roy & S. D. Poppitt

  6. Food and Bio-Based Products Group, AgResearch Ltd., Palmerston North, New Zealand

    N. C. Roy & D. Cameron-Smith

  7. Human Nutrition Unit, Department of Medicine, School of Biological Sciences, The University of Auckland, Auckland, New Zealand

    I. R. Sequeira & S. D. Poppitt

  8. School of Kinesiology, The University of British Columbia, Vancouver, Canada

    C. J. Mitchell

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  1. F. Ramzan
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Contributions

CJM, DCS, AMM, BD, SP and IR designed the research. CJM, AMM, FR, RFD and BD conducted the discovery phase, and SP and IR coordinated the validation phase. FR, CJM and VS conducted the statistical analysis. FR wrote the paper. All authors provided content and feedback on the manuscript. DCS has primary responsibility for the final content of the manuscript.

Corresponding author

Correspondence to D. Cameron-Smith.

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Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All procedures performed in the studies involving human participants were in accordance with the ethical standards of the Southern Health and Disability Ethics Committee (14/STH/184 and 16/STH/23) and University of Auckland Human Participants and Ethics Committee (014501).

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Informed consent was obtained from all individual participants included in the study.

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Ramzan, F., D’Souza, R.F., Durainayagam, B.R. et al. Circulatory miRNA biomarkers of metabolic syndrome. Acta Diabetol 57, 203–214 (2020). https://doi.org/10.1007/s00592-019-01406-6

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  • DOI: https://doi.org/10.1007/s00592-019-01406-6

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