Anales de la RANM

25 A N A L E S R A N M R E V I S T A F U N D A D A E N 1 8 7 9 S U P L E M E N T O I SIMPOSIO · JÓVENES INVESTIGADORES Libro de Abstracts An RANM. 2021;138(03).supl01: 25 - 54 Agradecimientos : Ministerio de Economía y Competitividad (MINNECO-FEDER, AGL2014- 55102-JIN), Universidad del País Vasco GIU18-173 e Instituto de Salud Carlos III (CIBERobn). Metabolic syndrome (MetS) is a cluster of risk factors characterized by hypertension, high triglyceride and low HDL levels, obesity and hyperglycaemia. Despite the fact that it is not a disease by itself, it is a major contributor to the appearance of cardiovas- cular diseases or type 2 diabetes mellitus, presen- ting an estimated prevalence of 30% in Western. Mechanistic processes underlying the develop- ment of MetS have not been fully elucidated. Some bioactive molecules naturally present in the diet have demonstrated to have beneficial effects in the management of the progression of the MetS; such is the case of phenolic compounds, which can be found in grapes. MicroRNAs (miRNAs) are small (usually 18-22 nucleotides long) non-coding RNAsable either to modify the translation process or to degrade mRNA. Almost 30% of human biochemical processes are estimated to be regulated by miRNAs. They can be found in peripherical blood, being considered easily accessible biomarkers. Thus, the aim of this study was to analyse the potential involvement of miRNAs in the mechanisms of action underlying the positive effect of a grape pomace (a polyphenol-rich byproduct from wine making) supplementation in patients with cardiometabolic risk and their role in the inter-individual variability in the response to that supplementation. To achieve that objective, an intervention randomized cross-over study was carried out, where the habitual diet of 49 subjects with at least two MetS factors was supplemented with grape pomace for 6 weeks. Then, participants were classified between responder and non-responders, according to the reduction in fasting insulin after the treatment ( Figure 1 ). Blood samples were extracted before and after the supplementation and were frozen until further analysis. mRNA was isolated from the samples and miRNA expression was determined through Next Generation Sequen- cing in a reduced number of individuals (n=6 per group). Differential expression of miRNAs changes where confirmed by RT-PCR in the whole cohort, and miRNAs` targets were assessed by bioinformatics analysis. It was observed that miR-222 and miR-30c, which are known to be related to insulin resistance and type 2 diabetes mellitus, were downregulated after the supplementation in responder subjects, being important contributors to the increase of glycolysis and glucose uptake in skeletal muscle ( Figure 2 ). Furthermore, patients who showed a positive response to the treatment presented higher concentration of miR-222, and thus, lower levels of pyruvate kinase and adiponectin receptor 1 ( Figure 3 ). Therefore, it can be concluded that mR-222 and miR-30c play a pivotal role in the beneficial effects in glucose homeostasis of a grape pomace supplementation in subjects with MetS. Moreover, miR-222 can be proposed as a biomarker to predict the response of these patients to the nutritional treatment with grape pomace. Acknowledgements : Spanish Ministry of Economy and Competitiveness (MINNECO-FEDER, grants AGL2014-55102-JIN), University of the Basque Country (GIU18-173) and Carlos III Research Institute (CIBERobn). Figure 1. Experimental design of the randomized croos-over study. Modified from Léniz A et al. Foods 2021, 10, 2059.