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Characterization of epigenetics biomarkers of type 2 diabetes mellitus: identification of potential therapeutic targets of n-3 polyunsaturated fatty acids


MicroRNAs (miRNAs) are involved in the control of energy metabolism and development of chronic diseases, such as obesity, T2DM, and metabolic syndrome. The identification of miRNAs associated with T2DM development is essential to understand the syndrome etiology and direct futher therapeutic studies. This project aims to characterize the expression profile of circulating exosomal miRNAs in T2DM subjects and identify the origin of these exosomal vesicles. We will evaluate: a) healthy individuals (normal glycemia and insulin sensitivity), b) glucose intolerant and insulin resistant subjects and c) newly diagnosed type 2 diabetic patients. The sample size will be calculated based on the initial results, considering alpha power of 0.05 and alterations of at least twice in expression of the miRNAs. The exosomal miRNAs profile will be evaluated by microarray PCR technique with quantitative validation by real time PCR. The characterization of the exosomal proteins will be established by proteomic analysis using mass spectrometry. Therefore, this study will be important for identifying and validating exossomal miRNAs as biomarkers of the T2DM development, as well as the origin of these exosomes and the modulation of this process by n-3 fatty acids, allowing the elucidation of the involvement of miRNAs on the diabetes development and the possible preventive and/or therapeutic effects of n-3 fatty acids. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MASI, LAUREANE N.; LOTUFO, PAULO A.; FERREIRA, FREDERICO M.; RODRIGUES, ALICE C.; SERDAN, TAMIRES D. A.; SOUZA-SIQUEIRA, TALITA; BRAGA, AECIO A.; SALDARRIAGA, MAGDA E. G.; ALBA-LOUREIRO, TATIANA C.; BORGES, FERNANDA T.; et al. Profiling plasma-extracellular vesicle proteins and microRNAs in diabetes onset in middle-aged male participants in the ELSA-Brasil study. PHYSIOLOGICAL REPORTS, v. 9, n. 3, . (14/21447-6, 19/25892-8, 15/12728-4, 17/03707-9, 18/00998-5)

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