Identification and validation of common molecular targets of hydroxytyrosol

Hydroxytyrosol (HT) is involved in healthful activities and is beneficial to lipid metabolism. Many investigations focused on finding tissue-specific targets of HT through the use of different omics approaches such as transcriptomics and proteomics. However, it is not clear which (if any) of the potential molecular targets of HT reported in different studies are concurrently affected in various tissues. Following the bioinformatic analyses of publicly available data from a selection of in vivo studies involving HT-supplementation, we selected differentially expressed lipid metabolism-related genes and proteins common to more than one study, for validation in rodent liver samples from the entire selection. Four miRNAs (miR-802-5p, miR-423-3p, miR-30a-5p, and miR-146b-5p) responded to HT supplementation. Of note, miR-802-5p was commonly regulated in the liver and intestine. Our premise was that, in an organ crucial for lipid metabolism such as the liver, consistent modulation should be found for a specific target of HT even if different doses and duration of HT supplementation were used in vivo. Even though our results show inconsistency regarding differentially expressed lipid metabolism-related genes and proteins across studies, we found Fgf21 and Rora as potential novel targets of HT. Omics approaches should be fine-tuned to better exploit the available databases.This research was funded by grants from the Spanish “Agencia Estatal de Investigación” and the European FEDER Funds to AD and RMH (AGL2016-78922-R); the Ministerio de Economía y Competitividad–Fondo Europeo de Desarrollo Regional (SAF2016-75441-R) and the Fondo Social Europeo–Gobierno de Aragón (B16_17R) to MAN and JO; the Fundación Ramón Areces (CIVP18A3888) to AD, JG-Z, JTC, MCC, FV and RMH; the CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERObn) to JAM, MPP, JO and MAN; and POR FESR 3S4H to FV. CIBERObn. is an initiative of the ISCIII, Spain. MCLH, LdP and MB R-R were recipients of contracts from the Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid, Fondo Social Europeo, and the Iniciativa de Empleo Juvenil YEI (PEJD-2016/BIO-2781, PEJD-2017-PRE/BIO-5100, and PEJD-2018-POST/BIO 8933), respectively.Peer reviewe