title: Chronic hydroxytyrosol feeding modulates glutathione-mediated oxido-reduction pathways in adipose tissue: a nutrigenomic study.
abstract: OBJECTIVE
  Hydroxytyrosol (HT) is the most prominent phenolic component of olives, olive oil, and their by-products, e.g. olive mill waste water. As the link between HT consumption (via extra virgin olive oil intake) and better cardiovascular prognosis is being scientifically validated, HT is entering the market as a potentially useful supplement for cardiovascular disease prevention. One of the target organs in cardiometabolic prevention is the adipose tissue, where inflammation, oxidative stress, and secretion of adipocytokines contribute to cardiovascular risk.
  
  
  RESULTS
  We explored the nutrigenomic effects of long-term supplementation with nutritionally-relevant doses of HT, i.e. 0.03 gm% - with specific reference to the adipose tissue and glutathione metabolism - and we explored underlying mechanisms in vitro. We show that HT modulates the antioxidant network in the adipose tissue, as mediated by glutathione (GSH) and associated enzymes. We also confirmed the GSH-modulating activities of HT in cultured adipocytes, where low, physiological HT concentrations were able to blunt the H2O2-induced GSH/GSSG alteration indicative of oxidative stress. In terms of surrogate markers of cardiovascular disease, we recorded significantly decreased circulating leptin concentrations in mice fed with HT as compared with controls.
  
  
  CONCLUSIONS
  HT - in nutritionally relevant amounts - is able to positively modulate the glutathione-driven antioxidant enzymatic machinery in the adipose tissue. Because HT is generally recognized as safe (GRAS) and exhibits an excellent safety profile in vitro and in vivo, its future employment as adjunct treatment of metabolic syndrome can be envisioned, pending specific trials.
authors.affiliation: Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA) - Food, CEI UAM+CSIC, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Giordano
authors.affiliation: Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA) - Food, CEI UAM+CSIC, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Dávalos
authors.affiliation: Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA) - Food, CEI UAM+CSIC, Madrid, Spain. Electronic address: francesco.visioli@imdea.org.
authors.forename: F
authors.initials: F
authors.lastname: Visioli
mesh_terms: D041721:3T3-L1 Cells; D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000188:drug therapy; D019587:Dietary Supplements; D005978:Glutathione / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000009:adverse effects; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D054647:Nutrigenomics / Q000379:methods*; D000069463:Olive Oil; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010938:Plant Oils / Q000008:administration & dosage; D012307:Risk Factors; D059467:Transcriptome
chemical_list: D054392:Adipokines; D000975:Antioxidants; D020738:Leptin; D000069463:Olive Oil; D010938:Plant Oils; C005975:3,4-dihydroxyphenylethanol; D006861:Hydrogen Peroxide; D005978:Glutathione; D010626:Phenylethyl Alcohol
keywords: Adipose tissue; Cardiovascular disease; Hydroxytyrosol; Mediterranean diet; Nutrigenomics