Hydroxytyrosol supplementation modulates the expression of miRNAs in rodents and in humans.
Dietary microRNAs (miRNAs) modulation could be important for health and wellbeing. Part of the healthful activities of polyphenols might be due to a modulation of miRNAs' expression. Among the most biologically active polyphenols, hydroxytyrosol (HT) has never been studied for its actions on miRNAs. We investigated whether HT could modulate the expression of miRNAs in vivo. We performed an unbiased intestinal miRNA screening in mice supplemented (for 8 weeks) with nutritionally relevant amounts of HT. HT modulated the expression of several miRNAs. Analysis of other tissues revealed consistent HT-induced modulation of only few miRNAs. Also, HT administration increased triglycerides levels. Acute treatment with HT and in vitro experiments provided mechanistic insights. The HT-induced expression of one miRNA was confirmed in healthy volunteers supplemented with HT in a randomized, double-blind and placebo-controlled trial. HT consumption affects specific miRNAs' expression in rodents and humans. Our findings suggest that the modulation of miRNAs' action through HT consumption might partially explain its healthful activities and might be pharmanutritionally exploited in current therapies targeting endogenous miRNAs. However, the effects of HT on triglycerides warrant further investigations.
Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA) Food, CEI UAM+CSIC, Madrid 28049, Spain.
Joao
J
Tomé-Carneiro
Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA) Food, CEI UAM+CSIC, Madrid 28049, Spain.
María Carmen
MC
Crespo
Department of Functional Biology (Physiology), University of Oviedo, Oviedo 33003, Spain; Universidad Autónoma de Chile, Santiago 7500912, Chile.
Eduardo
E
Iglesias-Gutierrez
Laboratory of Disorders of Lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA) Food, CEI UAM+CSIC, Madrid 28049, Spain.
Roberto
R
Martín
Laboratory of Disorders of Lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA) Food, CEI UAM+CSIC, Madrid 28049, Spain.
Judit
J
Gil-Zamorano
Department of Functional Biology (Physiology), University of Oviedo, Oviedo 33003, Spain.
Cristina
C
Tomas-Zapico
Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA) Food, CEI UAM+CSIC, Madrid 28049, Spain; Área de Bioquímica, Universidad de Castilla-La-Mancha, Toledo 45071, Spain.
Emma
E
Burgos-Ramos
Unidad de Cirugía Experimental, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid 28034, Spain.
Carlos
C
Correa
Servicio de Bioquímica Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid 28034, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid 28029, Spain.
Diego
D
Gómez-Coronado
Servicio de Bioquímica Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid 28034, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid 28029, Spain.
Miguel A
MA
Lasunción
Department of Biochemistry and Chemistry, Faculties of Pharmacy and Medicine, Universidad San Pablo CEU, Madrid 28668, Spain.
Emilio
E
Herrera
Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA) Food, CEI UAM+CSIC, Madrid 28049, Spain; Department of Molecular Medicine, University of Padova, Padova 35121, Italy. Electronic address: francesco.visioli@imdea.org.
Francesco
F
Visioli
Laboratory of Disorders of Lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA) Food, CEI UAM+CSIC, Madrid 28049, Spain. Electronic address: alberto.davalos@imdea.org.
Alberto
A
Dávalos
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009928:Organ Specificity; D009940:Organoids; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D046509:Tissue Culture Techniques
D035683:MicroRNAs; C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol
Dietary Supplementation; Hydroxytyrosol; Intestine; Lipids; miRNAs