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.

Hydroxytyrosol prevents metabolic impairment reducing hepatic inflammation and restoring duodenal integrity in a rat model of NAFLD / Pirozzi, Claudio; Lama, Adriano; Simeoli, Raffaele; Paciello, Orlando; Pagano, TERESA BRUNA; Mollica, MARIA PINA; Guida, Francesca Di; Russo, Roberto; Magliocca, Salvatore; BERNI CANANI, Roberto; MATTACE RASO, Giuseppina; Calignano, Antonio; Meli, Rosaria. - In: JOURNAL OF NUTRITIONAL BIOCHEMISTRY. - ISSN 0955-2863. - 30:(2016), pp. 108-115. [10.1016/j.jnutbio.2015.12.004.]

Hydroxytyrosol prevents metabolic impairment reducing hepatic inflammation and restoring duodenal integrity in a rat model of NAFLD.

PIROZZI, CLAUDIO
Primo
;
LAMA, ADRIANO;SIMEOLI, RAFFAELE;PACIELLO, ORLANDO;PAGANO, TERESA BRUNA;MOLLICA, MARIA PINA;RUSSO, ROBERTO;BERNI CANANI, ROBERTO;MATTACE RASO, GIUSEPPINA;CALIGNANO, ANTONIO;MELI, ROSARIA
2016

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.
2016
Hydroxytyrosol prevents metabolic impairment reducing hepatic inflammation and restoring duodenal integrity in a rat model of NAFLD / Pirozzi, Claudio; Lama, Adriano; Simeoli, Raffaele; Paciello, Orlando; Pagano, TERESA BRUNA; Mollica, MARIA PINA; Guida, Francesca Di; Russo, Roberto; Magliocca, Salvatore; BERNI CANANI, Roberto; MATTACE RASO, Giuseppina; Calignano, Antonio; Meli, Rosaria. - In: JOURNAL OF NUTRITIONAL BIOCHEMISTRY. - ISSN 0955-2863. - 30:(2016), pp. 108-115. [10.1016/j.jnutbio.2015.12.004.]
File in questo prodotto:
File Dimensione Formato  
HYDROXYTYROSOL PREVENTS METABOLIC IMPAIRMENT...pdf

accesso aperto

Tipologia: Documento in Post-print
Licenza: Dominio pubblico
Dimensione 1.17 MB
Formato Adobe PDF
1.17 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/641212
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 88
  • ???jsp.display-item.citation.isi??? 76
social impact