Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease  

作　　者：Sara Heebll Karen Louise Thomsen Steen B Pedersen Hendrik Vilstrup Jacob George Henning Grnbk 

机构地区：[1]Department of Hepatology and Gastroenterology,Aarhus University Hospital [2]Department of Endocrinology,Aarhus University Hospital [3]Storr Liver Unit,Westmead Millennium Institute,Westmead Hospital and University of Sydney

出　　处：《World Journal of Hepatology》2014年第4期188-198,共11页世界肝病学杂志（英文版）（电子版）

基　　金：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 Grnbk H by a research grant;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;Project grants 632630 and 1049857

摘　　要：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 RSVmediated 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.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 RSVmediated 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.

关 键 词：Non-alcoholic fatty liver disease NONALCOHOLIC STEATOHEPATITIS STEATOSIS RESVERATROL AMPactivated protein kinase Silent information regulation-2 homolog 1 ANTI-OXIDANTS Anti-inflammatory agents Animal studies CLINICAL trial 

分 类 号：R575.5[医药卫生—消化系统]