Sara Heebøll1,2,3, Rime Bahij El-Houri4, Ylva Erika Kristina Hellberg5, David Haldrup1,2, Steen Bønløkke Pedersen2,6, Niels Jessen7, Lars Porskjaer Christensen4, Henning Grønbaek1,2. 1. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. 2. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 3. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. 4. Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark. 5. Department of Pathology, Hvidovre Hospital, Hvidovre, Denmark. 6. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. 7. Department of Biochemical Pathology, Aarhus University Hospital, Aarhus, Denmark.
Abstract
BACKGROUND AND AIM: 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.
BACKGROUND AND AIM: 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: Danielle Pasquel; Aneta Doricakova; Hao Li; Sandhya Kortagere; Matthew D Krasowski; Arunima Biswas; William G Walton; Matthew R Redinbo; Zdenek Dvorak; Sridhar Mani Journal: Biochim Biophys Acta Date: 2016-02-23
Authors: David Haldrup; Sara Heebøll; Karen Louise Thomsen; Kasper Jarlhelt Andersen; Michelle Meier; Frank Viborg Mortensen; Jens Randel Nyengaard; Stephen Hamilton-Dutoit; Henning Grønbæk Journal: World J Hepatol Date: 2018-01-27