Hydroxytyrosol prevents metabolic impairment reducing hepatic inflammation and restoring duodenal integrity in a rat model of NAFLD |
| |
| Affiliation: | 1. Department of Pharmacy, University of Naples “Federico II”, 80131 Naples, Italy;2. Department of Veterinary Medicine and Animal Production, University of Naples “Federico II”, 80131 Naples, Italy;3. Department of Biology, University of Naples “Federico II”, 80131 Naples, Italy;4. 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;1. Food Technology Department, Agrotecnio Research Center, Escola Tècnica Superior d''Enginyeria Agrària, University of Lleida, Avda/Alcalde Rovira Roure 191, 25198 Lleida, Spain;2. Department of Medicine, Facultat de Medicina, University of Lleida, Avda/Alcalde Rovira Roure 80, 25198 Lleida, Spain;3. Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Unit of Lipids and Atherosclerosis Research (URLA), Centro de Investigación Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), University Hospital Sant Joan, IISPV, Technological Center of Nutrition and Health (CTNS), Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Sant Llorenç, 21, 43201 Reus, Spain;1. Research Institute of Atherosclerotic Disease, Xi''an Jiaotong University Cardiovascular Research Center, Xi''an 710061, China;2. Laboratory Animal Center, Xi''an Jiaotong University Health Science Center, Xi''an 710061, China;3. Department of Pharmacology, Xi''an Jiaotong University Health Science Center, Xi''an 710061, China;4. Department of Pharmacy, Yangquan Coalmine Group General Hospital, Yangquan 045000, China;5. Department of Pharmacy, the First Affiliated Hospital of Xi''an Medical College, Xi''an 710061, China;6. School of Pharmacy, Xi''an Jiaotong University Health Science Center, Xi''an 710061, China |
| |
| 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. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
