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Dietary bovine milk miRNAs transported in extracellular vesicles are partially stable during GI digestion, are bioavailable and reach target tissues but need a minimum dose to impact on gene expression.
López de Las Hazas, María-Carmen; Del Pozo-Acebo, Lorena; Hansen, Maria S; Gil-Zamorano, Judit; Mantilla-Escalante, Diana C; Gómez-Coronado, Diego; Marín, Francisco; Garcia-Ruiz, Almudena; Rasmussen, Jan T; Dávalos, Alberto.
Afiliación
  • López de Las Hazas MC; Laboratory of Epigenetics of Lipid Metabolism, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain.
  • Del Pozo-Acebo L; Laboratory of Epigenetics of Lipid Metabolism, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain.
  • Hansen MS; Department of Molecular Biology and Genetics, Aarhus University, 8000, Aarhus, Denmark.
  • Gil-Zamorano J; Laboratory of Epigenetics of Lipid Metabolism, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain.
  • Mantilla-Escalante DC; Laboratory of Epigenetics of Lipid Metabolism, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain.
  • Gómez-Coronado D; Department of Biochemistry-Research, Hospital Universitario Ramón y Cajal, IRYCIS, 28034, Madrid, Spain.
  • Marín F; CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28034 Madrid, Spain.
  • Garcia-Ruiz A; Department of Applied Chemistry-Physics, Faculty of Science, University Autónoma of Madrid, 28049, Madrid, Spain.
  • Rasmussen JT; Laboratory of Epigenetics of Lipid Metabolism, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain.
  • Dávalos A; Department of Molecular Biology and Genetics, Aarhus University, 8000, Aarhus, Denmark.
Eur J Nutr ; 61(2): 1043-1056, 2022 Mar.
Article en En | MEDLINE | ID: mdl-34716465
PURPOSE: Extracellular RNAs are unstable and rapidly degraded unless protected. Bovine-milk extracellular vesicles (EVs) confer protection to dietary miRNAs, although it remains unclear whether this importantly improves their chances of reaching host target cells to exert biological effects. METHODS: Caco-2, HT-29, Hep-G2 and FHs-74 cell lines were exposed to natural/labelled milk EVs to evaluate cellular uptake. Five frequently reported human milk miRNAs (miR-146b-5p, miR-148a-3p, miR-30a-5p, miR-26a-5p, and miR-22-3p) were loaded into EVs. The intracellular concentration of each miRNA in cells was determined. In addition, an animal study giving an oral dose of loaded EVs in C57BL6/ mice were performed. Gene expression regulation was assessed by microarray analysis. RESULTS: Digestive stability analysis showed high overall degradation of exogenous miRNAs, although EV-protected miRNAs better resisted gastrointestinal digestion compared to free miRNAs (tenfold higher levels). Importantly, orally delivered EV-loaded miRNAs reached host organs, including brain, in mice. However, no biological effect has been identified. CONCLUSION: Milk EVs protect miRNAs from degradation and facilitate cellular uptake. miRNA concentration in EVs from bovine milk might be insufficient to produce gene modulation. Nevertheless, sizable amounts of exogenous miRNAs may be loaded into EVs, and orally delivered EV-loaded miRNAs can reach tissues in vivo, increasing the possibility of exerting biological effects. Further investigation is justified as this could have an impact in the field of nutrition and health (i.e., infant formulas elaboration).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Vesículas Extracelulares Límite: Animals / Humans Idioma: En Revista: Eur J Nutr Asunto de la revista: CIENCIAS DA NUTRICAO Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Alemania
Texto completo
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Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Vesículas Extracelulares Límite: Animals / Humans Idioma: En Revista: Eur J Nutr Asunto de la revista: CIENCIAS DA NUTRICAO Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Alemania