title: Hydroxytyrosol prevents metabolic impairment reducing hepatic inflammation and restoring duodenal integrity in a rat model of NAFLD.
abstract: The potential mechanisms of action of polyphenols in nonalcoholic fatty liver disease (NAFLD) are overlooked. Here, we evaluate the beneficial therapeutic effects of hydroxytyrosol (HT), the major metabolite of the oleuropein, in a nutritional model of insulin resistance (IR) and NAFLD by high-fat diet. Young male rats were divided into three groups receiving (1) standard diet (STD; 10.5% fat), (2) high-fat diet (HFD; 58.0% fat) and (3) HFD+HT (10 mg/kg/day by gavage). After 5 weeks, the oral glucose tolerance test was performed, and at 6th week, blood sample and tissues (liver and duodenum) were collected for following determinations. The HT-treated rats showed a marked reduction in serum AST, ALT and cholesterol and improved glucose tolerance and insulin sensitivity, reducing homeostasis model assessment index. HT significantly corrected the metabolic impairment induced by HFD, increasing hepatic peroxisome proliferator activated receptor PPAR-α and its downstream-regulated gene fibroblast growth factor 21, the phosphorylation of acetyl-CoA carboxylase and the mRNA carnitine palmitoyltransferase 1a. HT also reduced liver inflammation and nitrosative/oxidative stress decreasing the nitrosylation of proteins, reactive oxygen species production and lipid peroxidation. Moreover, HT restored intestinal barrier integrity and functions (fluorescein isothiocyanate-dextran permeability and mRNA zona occludens ZO-1). Our data demonstrate the beneficial effect of HT in the prevention of early inflammatory events responsible for the onset of IR and steatosis, reducing hepatic inflammation and nitrosative/oxidative stress and restoring glucose homeostasis and intestinal barrier integrity.
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Pirozzi
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Lama
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Simeoli
authors.affiliation: Department of Veterinary Medicine and Animal Production, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Orlando
authors.initials: O
authors.lastname: Paciello
authors.affiliation: Department of Veterinary Medicine and Animal Production, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Teresa Bruna
authors.initials: TB
authors.lastname: Pagano
authors.affiliation: Department of Biology, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Maria Pina
authors.initials: MP
authors.lastname: Mollica
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Guida
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Russo
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Magliocca
authors.affiliation: Department of Translational Medical Science and European Laboratory for the Investigation of Food Induced Diseases and CEINGE Advanced Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Roberto Berni
authors.initials: RB
authors.lastname: Canani
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Giuseppina Mattace
authors.initials: GM
authors.lastname: Raso
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Calignano
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy. Electronic address: meli@unina.it.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Meli
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004386:Duodenum / Q000503:physiopathology; D006505:Hepatitis / Q000503:physiopathology*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000503:physiopathology / Q000628:therapy*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats
chemical_list: C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol
keywords: Duodenal permeability; Glucose tolerance; Insulin resistance; Liver inflammation; Nonalcoholic fatty liver disease; Olive oil polyphenols