title: Effect of resveratrol on experimental non-alcoholic fatty liver disease depends on severity of pathology and timing of treatment.
abstract: OBJECTIVE
  Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. Resveratrol (RSV) prevents the development of steatosis in a number of experimental fatty liver (non-alcoholic fatty liver [NAFL]) models, but the preventive or therapeutic effects on experimental NASH are not yet clarified, and clinical results on non-alcoholic fatty liver disease are ambiguous. Thus, we aimed to compare the RSV-mediated preventive and therapeutic effects on experimental NAFL and NASH.
  
  
  METHODS
  We used a high-fat (HF) diet to generate a rat NAFL model and a high-fat, high-cholesterol (HFC) diet to generate a rat NASH model. The preventive and therapeutic potential of RSV was tested by adding RSV to the HF and HFC diet from study start or after 1 week of the diets. Animals were sacrificed after 8 weeks with appropriate controls. Blood and liver were harvested for analysis, including measurement of RSV metabolites.
  
  
  RESULTS
  Resveratrol reduced the development of histological steatosis (P = 0.03) and partly triglyceride accumulation (fold change reduced from 3.6 to 2.4, P = 0.08) in the male NAFL model, although effects were moderate. In NASH prevention, RSV reduced the accumulation of triglyceride in hepatic tissue (P < 0.01), while there was no effect on biochemical, histopathological, or transcriptional NASH changes. Further, RSV had no therapeutic effect on established NASH. We found RSV metabolites but no parent RSV in serum or liver tissue, confirming low bioavailability.
  
  
  CONCLUSIONS
  These experimental findings suggest that a weak hepatic benefit of RSV treatment is seen in prevention of steatosis only.
authors: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.|Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.|Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors: Sara
authors: http://orcid.org/0000-0002-3474-0379
authors: S
authors: Heebøll
authors: Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark.
authors: Rime Bahij
authors: RB
authors: El-Houri
authors: Department of Pathology, Hvidovre Hospital, Hvidovre, Denmark.
authors: Ylva Erika Kristina
authors: YE
authors: Hellberg
authors: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.|Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: David
authors: D
authors: Haldrup
authors: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.|Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors: Steen Bønløkke
authors: SB
authors: Pedersen
authors: Department of Biochemical Pathology, Aarhus University Hospital, Aarhus, Denmark.
authors: Niels
authors: N
authors: Jessen
authors: Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark.
authors: Lars Porskjaer
authors: LP
authors: Christensen
authors: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.|Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: Henning
authors: H
authors: Grønbaek
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism; D001682:Biological Availability; D004195:Disease Models, Animal; D005260:Female; D008099:Liver / Q000378:metabolism; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D014280:Triglycerides; D000077185:Resveratrol
keywords: experimental animal models; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; resveratrol