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One-year dietary supplementation with walnuts modifies exosomal miRNA in elderly subjects

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

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.

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Abbreviations

c-miRNAs:

Circulating-miRNAs

EVs:

Extracellular vesicles

miRNAs:

MicroRNAs

NTA:

Nanoparticle tracking analysis

qRT-PCR:

Quantitative real-time PCR

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Acknowledgements

We thank the volunteers who participated in this study, the Hector Peinado Lab (Madrid) for the use of NanoSight equipment and the Solmeglas S. L. company (Madrid) for the use of ZetaView® equipment. CIBEROBN is an initiative of Instituto de Salud Carlos III, Spain. We thank the Quantification and Molecular Characterization Unit (IRYCIS) for their technical help.

Funding

This research was supported in part by a grant from the California Walnut Commission, Folsom, CA, USA. The funding agency had no involvement in any stage of the study design, research or writing of the manuscript. The work is also supported by Fundación Ramón Areces (CIVP18A3888) Madrid, Spain; the Instituto de Salud Carlos III-Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (grant PI15/01014 and PI18/01152), and the Spanish Agencia Estatal de Investigación and European Feder Funds (AGL2016-78922-R, PID2019-109369RB-I00, RTI2018-093873-A-I00 and BIO2017-86500-R). AS-V is recipient of the Instituto de Salud Carlos III Miguel Servet II fellowship (grant CP II 17/00029). MCLH and LdP were supported by a postdoctoral research contract funded by the community of Madrid and European Union (PEJD-2016/BIO-2781 and PEJD-2017-PRE/BIO-5100, respectively). D.C.M.-E. is a fellow of “Centro de Estudios Interdisciplinarios Básicos y Aplicados” (CEIBA), Colombia, through the program “Bolívar Gana con Ciencia”. Also, A.G.-R. acknowledges the Marie Curie AMAROUT-II Europe Program (Grant Agreement No. 291803).

Author information

Author notes

  1. María-Carmen López de las Hazas, Judit Gil-Zamorano and Montserrat Cofán have contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain

    María-Carmen López de las Hazas, Judit Gil-Zamorano, Diana C. Mantilla-Escalante, Almudena Garcia-Ruiz, Lorena del Pozo-Acebo & Alberto Dávalos

  2. Lipid Clinic, Endocrinology and Nutrition Service, Institut d´Investigacions Biomèdiques August Pi i Sunyer, 08036, Barcelona, Spain

    Montserrat Cofán, Mercè Serra-Mir, Monica Doménech, Cinta Valls-Pedret & Emilio Ros

  3. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain

    Montserrat Cofán, Oscar Pastor & Emilio Ros

  4. Servicio de Bioquímica Clínica (UCA-CCM), Hospital Ramón y Cajal-IRYCIS, 28034, Madrid, Spain

    Oscar Pastor

  5. Department of Molecular Biology, UAM, 28049, Madrid, Spain

    María Yañez-Mo & Carla Mazzeo

  6. Centro de Biología Molecular Severo Ochoa (CBM-SO), Instituto de Investigación Sanitaria Princesa (IIS-IP), 28049, Madrid, Spain

    María Yañez-Mo & Carla Mazzeo

  7. Center for Nutrition, Healthy Lifestyle and Disease Prevention, School of Public Health, Loma Linda University, Loma Linda, CA, 92350, USA

    Sujatha Rajaram & Joan Sabaté

  8. Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, 08003, Spain

    Aleix Sala-Vila

  9. Hospital del Mar Medical Research Institute, IMIM, Dr. Aiguader 88, 08003, Barcelona, Spain

    Aleix Sala-Vila

Authors
  1. María-Carmen López de las Hazas
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  2. Judit Gil-Zamorano
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Contributions

JS, SR, ER, AS-V and AD designed the study. MC, MS-M, IR, T-MF-S, MD, CV-P recruited and obtained the samples. MCLH, JG-Z, DME, LDP, AGR and AD, performed miRNA analysis. MCLH, CM, and MYM contributed to the NTA analysis, MCLH, JG-Z and DCME analyzed data. OP perform the lipidomic analysis. MCLH and DCME performed bioinformatic analysis. MCLH, ER, AS-V and AD wrote the manuscript. All authors reviewed and accepted the manuscript.

Corresponding authors

Correspondence to Aleix Sala-Vila or Alberto Dávalos.

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Conflict of interest

AS-V, SR, JS, and ER have received research funding through their institutions from the California Walnut Commission, Folsom, CA, USA. JS and ER were nonpaid members of California Walnut Commission Scientific Advisory Council. ER was a paid member of the California Walnut Commission Health Research Advisory Group. AS-V has received support from California Walnut Commission to attend professional meetings. All the other authors declare no competing financial interests.

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López de las Hazas, MC., Gil-Zamorano, J., Cofán, M. et al. One-year dietary supplementation with walnuts modifies exosomal miRNA in elderly subjects. Eur J Nutr 60, 1999–2011 (2021). https://doi.org/10.1007/s00394-020-02390-2

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  • DOI: https://doi.org/10.1007/s00394-020-02390-2

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