Mol. Nutr. Food Res. 2013, 00, 1–12 1 DOI 10.1002/mnfr.201200613 REVIEW Up-to date knowledge on the in vivo transcriptomic effect of the Mediterranean diet in humans Valentini Konstantinidou 1∗ , Maria-Isabel Covas 2∗ , Rosa Sola 1 and Montserrat Fit ´ o 2 1 Research Unit on Lipids and Atherosclerosis, Hospital Universitari Sant Joan, IISPV, Universitat Rovira i Virgili and CIBER Diabetes and Associated Metabolic Disorders, (CIBERDEM), Reus, Spain 2 Cardiovascular Risk and Nutrition Research Group, Mar Institute of Medical Research (IMIM), CIBER de Fisiopatolog´ ıa de la Obesidad y la Nutrici ´ on (CIBEROBN), Barcelona, Spain The present review discusses and summarizes the up-to-date body of knowledge concerning human nutrigenomic studies with Mediterranean diet (MedDiet) and olive oil (OO) interven- tions, at real-life doses and conditions. A literature review was carried out until March 2012. Original articles assessing the nutrigenomic effect of the MedDiet and its main source of fat, OO, on gene expression were selected. State-of-the-art data in this field, although scarce, are promising. Despite a great diversity among studies, the attributed health benefits of the MedDiet and its components, such as OO, could be explained by a transcriptomic effect on atherosclerosis, inflammation, and oxidative stress-related genes (i.e. ADRB2, IL7R, IFN, MCP1, TNF). Gene expression changes toward a protective mode were often associated with an improvement in systemic markers for oxidation and inflammation. The suggested underly- ing molecular pathways responsible for these changes, and the extent to which evidence exists of a MedDiet and OO nutrigenomic effect, are also discussed. Keywords: Molecular pathways / Nutrigenomics / Olive oil / Polyphenols Received: September 17, 2012 Revised: December 12, 2012 Accepted: December 15, 2012 Correspondence: Dr. Montserrat Fit ´ o, Cardiovascular Risk and Nu- trition Group, IMIM, PRBB, Carrer Doctor Aiguader, 88, 08003 Barcelona, Spain E-mail: mfito@imim.es Fax: +34-933-16-07-96 Abbreviations: ADAM17, ADAM metallopeptidase domain 17; ADRB2, adrenoreceptor beta 2; ALDH1A1, aldehyde de- hydrogenase 1 family, member A1; ALOX5AP, arachidonate 5-lipoxygenase-activating protein; ARHGAP15, Rho GT- Pase activating protein 15; BiP/Grp78, glucose-regulated protein, 78kDa; BIRC1, NLR family, apoptosis inhibitory protein; CCL5/RANTES, chemokine (C-C motif) ligand 5; CD40/CD40L, CD40 antigen ligand; COX2, cyclooxigenase- 2; ERCC5, DNA excision repair protein; GLUT4, glucose transporter 4; JNK1, Jun N-terminal kinase 1; IKB, NF- kappa-B inhibitor alpha; IKKb, inhibitor of nuclear factor kappa-B kinase subunit beta; IL7R, interleukin 7 receptor; IFN, interferon gamma; KEAP1, kelch-like ECH-associated protein 1; LEP, leptin; LIAS, lipoic acid synthetase; LPL, lipoprotein lipase; LRP1, low- density lipoprotein receptor-related protein; MCP1, monocyte chemoattractant protein 1; MedDiet, Mediterranean diet; MMP9, matrix metallopeptidase 9; NFB, nuclear factor NF-kappa-B; NRF2, nuclear factor (erythroid-derived 2)-like 2; OGT, O-linked N-acetylglucosamine (GlcNAc) transferase; PBMCs, peripheral blood mononuclear cells; PPARBP, peroxisome proliferator- activated receptor-binding prote´ ına; POLK, polymerase ; 1 Introduction Since the 1960s, the Mediterranean diet (MedDiet) refers to dietary patterns found in olive-growing areas of the Mediter- ranean region [1–3]. The MedDiet is a primordial dietary pat- tern, which consists of diet variants depending on each region in the Mediterranean basin. All MedDiet variants may have their own peculiarities, but olive oil (OO) is considered the hallmark of this dietary pattern and its main source of fat [2]. The MedDiet is characterized by (i) a high consumption of vegetables, legumes, fruits, and cereals; (ii) a regular but mod- erate wine intake; (iii) moderate consumption of fish; (iv) low consumption of meat; and (v) low-to-moderate intake of dairy products [3]. Total lipid intake may be high, around or in p22 phox and p47 phox , NADPH oxidase subunits; RAC2, rho family, small GTP binding protein Rac2; SOD1, superoxide dismutase 1; SOD2, superoxide dismutase 2; sXBP1, X-box binding protein 1; TNF, tumor necrosis factor ; TNFSF10, tumor necrosis factor (ligand) superfamily, member 10; TRXR, thioredoxin reductase; USP48, ubiquitin-specific peptidase 48; VOO, vir- gin olive oil; XRCC5, x-ray repair complementing defective repair ∗ Both authors contributed equally to the work. C  2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.mnf-journal.com