Miranda, J. (Jonatan)

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    Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk
    (BioMed Central, 2013) Martinez-Gonzalez, M.A. (Miguel Ángel); Juanola-Falgarona, M. (Martí); Miranda, J. (Jonatan); Bullo, M. (Monica); Portillo, M.P. (María P.); Casas, R. (Rosa); Estruch, R. (Ramón); Salas-Salvado, J. (Jordi)
    BACKGROUND: Vitamin K has been related to glucose metabolism, insulin sensitivity and diabetes. Because inflammation underlies all these metabolic conditions, it is plausible that the potential role of vitamin K in glucose metabolism occurs through the modulation of cytokines and related molecules. The purpose of the study was to assess the associations between dietary intake of vitamin K and peripheral adipokines and other metabolic risk markers related to insulin resistance and type 2 diabetes mellitus. METHODS: Cross-sectional and longitudinal assessments of these associations in 510 elderly participants recruited in the PREDIMED centers of Reus and Barcelona (Spain). We determined 1-year changes in dietary phylloquinone intake estimated by food frequency questionnaires, serum inflammatory cytokines and other metabolic risk markers. RESULTS: In the cross-sectional analysis at baseline no significant associations were found between dietary phylloquinone intake and the rest of metabolic risk markers evaluated, with exception of a negative association with plasminogen activator inhibitor-1. After 1-year of follow-up, subjects in the upper tertile of changes in dietary phylloquinone intake showed a greater reduction in ghrelin (-15.0%), glucose-dependent insulinotropic peptide (-12.9%), glucagon-like peptide-1 (-17.6%), IL-6 (-27.9%), leptin (-10.3%), TNF (-26.9%) and visfatin (-24.9%) plasma concentrations than those in the lowest tertile (all p<0.05). CONCLUSION: These results show that dietary phylloquinone intake is associated with an improvement of cytokines and other markers related to insulin resistance and diabetes, thus extending the potential protection by dietary phylloquinone on chronic inflammatory diseases. TRIAL REGISTRATION: http://www.controlled-trials.com as ISRCTN35739639.
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    High-throughput sequencing of microRNAs in peripheral blood mononuclear cells: identification of potential weight loss biomarkers
    (Public Library of Science, 2013) Martinez, J.A. (José Alfredo); Miranda, J. (Jonatan); Milagro-Yoldi, F.I. (Fermín Ignacio); Portillo, M.P. (María P.); Campión-Zabalza, J. (Javier); Fernandez-Quintela, A. (Alfredo)
    INTRODUCTION: MicroRNAs (miRNAs) are being increasingly studied in relation to energy metabolism and body composition homeostasis. Indeed, the quantitative analysis of miRNAs expression in different adiposity conditions may contribute to understand the intimate mechanisms participating in body weight control and to find new biomarkers with diagnostic or prognostic value in obesity management. OBJECTIVE: The aim of this study was the search for miRNAs in blood cells whose expression could be used as prognostic biomarkers of weight loss. METHODS: Ten Caucasian obese women were selected among the participants in a weight-loss trial that consisted in following an energy-restricted treatment. Weight loss was considered unsuccessful when <5% of initial body weight (non-responders) and successful when >5% (responders). At baseline, total miRNA isolated from peripheral blood mononuclear cells (PBMC) was sequenced with SOLiD v4. The miRNA sequencing data were validated by RT-PCR. RESULTS: Differential baseline expression of several miRNAs was found between responders and non-responders. Two miRNAs were up-regulated in the non-responder group (mir-935 and mir-4772) and three others were down-regulated (mir-223, mir-224 and mir-376b). Both mir-935 and mir-4772 showed relevant associations with the magnitude of weight loss, although the expression of other transcripts (mir-874, mir-199b, mir-766, mir-589 and mir-148b) also correlated with weight loss. CONCLUSIONS: This research addresses the use of high-throughput sequencing technologies in the search for miRNA expression biomarkers in obesity, by determining the miRNA transcriptome of PBMC. Basal expression of different miRNAs, particularly mir-935 and mir-4772, could be prognostic biomarkers and may forecast the response to a hypocaloric diet.
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    The combination of resveratrol and CLA does not increase the delipidating effect of each molecule in 3T3-L1 adipocytes
    (Sociedad Española de Nutrición Parenteral y Enteral, 2011) Martinez, J.A. (José Alfredo); Arias, N. (Noemi); Simon, E. (E.); Miranda, J. (Jonatan); Milagro-Yoldi, F.I. (Fermín Ignacio); Churruca, I. (I.); Lasa, A. (A.); Portillo, M.P. (María P.)
    Introduction: Trans-10, cis-12 conjugated linoleic acid (CLA) and resveratrol have been shown to reduce TG content in cultured 3T3-L1 adipocyte acting on different pathways. In recent years, the method of simultaneously targeting several signal transduction pathways with multiple natural products in order to achieve additive or synergistic effects has been tested. However, the combined effect of both molecules on lipid metabolism has not been described before. Objective: The aim of the present work was to analyze the effect of the combination of trans-10, cis-12 CLA and resveratrol on TG accumulation as well as on FAS, HSL and ATGL expression in 3T3-L1 mature adipocytes, in order to assess a potential interaction between both molecules. Methods: For this purpose, 3T3-L1 mature adipocytes were treated with the two molecules, both separately and combined, in 10 and 100 μM for 20 hours. TG content and FAS, ATGL and HSL expression were measured by spectrophotometry and Real Time RT-PCR respectively. Results: Both doses of CLA and 100 M resveratrol decreased TG content in mature adipocytes. The combination of both molecules reduced TG accumulation to the same extent as each one separately. No change in FAS and HSL mRNA levels after CLA and resveratrol treatment was observed. ATGL was not modified by CLA but it was increased by resveratrol and by the combination. This combination did not increase the effect caused by resveratrol on its own. Conclusion: Lipolysis increase via ATGL is involved in the TG reduction induced by resveratrol and the combination of both molecules. The combination of these two molecules does not increase the efficacy of each molecule separately in mature adipocytes and thus it does not represent an advantage for obesity treatment or prevention.