Review
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World J Hepatol. Apr 27, 2014; 6(4): 188-198
Published online Apr 27, 2014. doi: 10.4254/wjh.v6.i4.188
Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease
Sara Heebøll, Karen Louise Thomsen, Steen B Pedersen, Hendrik Vilstrup, Jacob George, Henning Grønbæk
Sara Heebøll, Karen Louise Thomsen, Hendrik Vilstrup, Henning Grønbæk, Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8000 Aarhus C, Denmark
Steen B Pedersen, Department of Endocrinology, Aarhus University Hospital, 8000 Aarhus C, Denmark
Jacob George, Storr Liver Unit, Westmead Millennium Institute, Westmead Hospital and University of Sydney, Westmead, NSW 2145, Australia
Author contributions: Heebøll S searched the literature; Heebøll S and Grønbæk H prepared the manuscript; the remaining authors revised the manuscript and gave intellectual and editorial input; all authors approved the final version of submitted manuscript.
Supported by Aarhus University and the Danish Council for Independent Research, Medical Sciences, No. 11-107912; The Danish Strategic Research Council has supported the LIRMOI study on RSV effects in NAFLD and metabolic diseases, No. 10-093499; The NOVO Nordisk Foundation has supported Grønbæk H by a research grant; George J was supported by the Robert W; Storr Bequest to the Sydney Medical; Foundation, University of Sydney; a National Health and Medical Research Council of Australia (NHMRC) Program Grant No. 1053206 and Project grants 632630 and 1049857
Correspondence to: Henning Grønbæk, MD, PhD, Professor of Experimental Hepatology, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark. henning.gronbaek@aarhus.rm.dk
Telephone: +45-7846-1546   Fax: +45-7846-2860
Received: October 30, 2013
Revised: January 22, 2014
Accepted: February 20, 2014
Published online: April 27, 2014
Processing time: 201 Days and 17.4 Hours
Abstract

The prevalence of obesity and related conditions like non-alcoholic fatty liver disease (NAFLD) is increasing worldwide and therapeutic options are limited. Alternative treatment options are therefore intensively sought after. An interesting candidate is the natural polyphenol resveratrol (RSV) that activates adenosinmonophosphate-activated protein kinase (AMPK) and silent information regulation-2 homolog 1 (SIRT1). In addition, RSV has known anti-oxidant and anti-inflammatory effects. Here, we review the current evidence for RSV-mediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis (NASH) pathogenesis with respect to free fatty acid (FFA) flux from adipose tissue, hepatic de novo lipogenesis, inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits. We review the in vivo evidence from animal studies and clinical trials. The abundance of animal studies reports a decrease in hepatic triglyceride accumulation, liver weight and a general improvement in histological fatty liver changes, along with a reduction in circulating insulin, glucose and lipid levels. Some studies document AMPK or SIRT1 activation, and modulation of relevant markers of hepatic lipogenesis, inflammation and oxidation status. However, AMPK/SIRT1-independent actions are also likely. Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes. Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients.

Keywords: Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Steatosis; Resveratrol; AMP-activated protein kinase; Silent information regulation-2 homolog 1; Anti-oxidants; Anti-inflammatory agents; Animal studies; Clinical trial

Core tip: The prevalence of obesity and related conditions like non-alcoholic fatty liver disease (NAFLD) is increasing. Therapeutic options are limited and alternative treatment options are sought after. An interesting candidate is resveratrol (RSV), a known AMP-activated protein kinase and silent information regulation-2 homolog 1 activator with anti-oxidant and anti-inflammatory properties. Here, we review the current evidence for RSV-mediated effects and address the different aspects of NAFLD and non-alcoholic steatohepatitis pathogenesis. We review the in vivo evidence from animal studies and clinical trials. Uniformly, animal studies report a decrease in hepatic triglyceride accumulation and improvements in histological fatty liver changes, whereas results from the few clinical trials are equivocal.