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...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.展开更多
Liver fibrosis represents a response to chronic liver injury.Metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases,both wi...Liver fibrosis represents a response to chronic liver injury.Metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases,both with increasing incidence.Therefore,there is a great impetus for development of agents targeting these conditions.Accumulating data on possible treatment options for liver fibrosis are emerging in the literature.However,despite extensive research and much effort in the field,approved agents for liver fibrosis are still lacking.In this critical review,we have summarized the main data about specific treatment options for liver fibrosis gained from ongoing clinical trials,with an emphasis on efficacy and safety of these agents.展开更多
基金Supported by Aarhus University and the Danish Council for Independent Research,Medical Sciences,No.11-107912The Danish Strategic Research Council has supported the LIRMOI study on RSV effects in NAFLD and metabolic diseases,No.10-093499+5 种基金The NOVO Nordisk Foundation has supported Grnbk H by a research grantsupported by the Robert WStorr Bequest to the Sydney MedicalFoundation,University of Sydneya National Health and Medical Research Council of Australia (NHMRC) Program Grant No.1053206Project grants 632630 and 1049857
文摘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.
基金funded by grant from Croatian Ministry of Science and Education dedicated to multi-year institutional funding of scientific activity at the J.J.Strossmayer University of Osijek,Osijek,Croatia—grant number:IP6-MEFOS-2019(to R.S.).
文摘Liver fibrosis represents a response to chronic liver injury.Metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases,both with increasing incidence.Therefore,there is a great impetus for development of agents targeting these conditions.Accumulating data on possible treatment options for liver fibrosis are emerging in the literature.However,despite extensive research and much effort in the field,approved agents for liver fibrosis are still lacking.In this critical review,we have summarized the main data about specific treatment options for liver fibrosis gained from ongoing clinical trials,with an emphasis on efficacy and safety of these agents.
