One-year dietary supplementation with walnuts modifies exosomal miRNA in elderly subjects
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ORIGINAL CONTRIBUTION
One‑year dietary supplementation with walnuts modifies exosomal miRNA in elderly subjects María‑Carmen López de las Hazas1 · Judit Gil‑Zamorano1 · Montserrat Cofán2,3 · Diana C. Mantilla‑Escalante1 · Almudena Garcia‑Ruiz1 · Lorena del Pozo‑Acebo1 · Oscar Pastor3,4 · María Yañez‑Mo5,6 · Carla Mazzeo5,6 · Mercè Serra‑Mir2 · Monica Doménech2 · Cinta Valls‑Pedret2 · Sujatha Rajaram7 · Joan Sabaté7 · Emilio Ros2,3 · Aleix Sala‑Vila8,9 · Alberto Dávalos1 Received: 5 May 2020 / Accepted: 14 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Epidemiological studies and clinical trials support the association of nut consumption with a lower risk of prevalent non-communicable diseases, particularly cardiovascular disease. However, the molecular mechanisms underlying nut benefits remain to be fully described. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and play a pivotal role in health and disease. Exosomes are extracellular vesicles released from cells and mediate intercellular communication. Whether nut consumption modulates circulating miRNAs (c-miRNAs) transported in exosomes is poorly described. Methods Cognitively healthy elderly subjects were randomized to either control (n = 110, abstaining from walnuts) or daily supplementation with walnuts (15% of their total energy, ≈30–60 g/day, n = 101) for 1-year. C-miRNAs were screened in exosomes isolated from 10 samples, before and after supplementation, and identified c-miRNA candidates were validated in the whole cohort. In addition, nanoparticle tracking analysis and lipidomics were assessed in pooled exosomes from the whole cohort. Results Exosomal hsa-miR-32-5p and hsa-miR-29b-3p were consistently induced by walnut consumption. No major changes in exosomal lipids, nanoparticle concentration or size were found. Conclusion Our results provide novel evidence that certain c-miRNAs transported in exosomes are modulated by walnut consumption. The extent to which this finding contributes to the benefits of walnuts deserves further research. Keywords c-miRNA · Dietary intervention · Exosomes · Lipidomics · Walnuts Abbreviations c-miRNAs Circulating-miRNAs EVs Extracellular vesicles miRNAs MicroRNAs NTA Nanoparticle tracking analysis qRT-PCR Quantitative real-time PCR María-Carmen López de las Hazas, Judit Gil-Zamorano and Montserrat Cofán have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00394-020-02390-2) contains supplementary material, which is available to authorized users. * Aleix Sala‑Vila [email protected] * Alberto Dávalos [email protected] Extended author information available on the last page of the article
Introduction Nuts are an energy-dense food composed by unsaturated fatty acids [1–3] and other phytochemicals such as vitamin E, phytosterols and polyphenols [1]. A robust body of evidence from prospective studies suggests that sustained nut consumption (30–42.5 g/day [
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