Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the adult population and is now a major cause of liver disease-related premature illness and deaths in the world. Treatment is largely based on lifestyle modification, which is difficult to achieve in most patients. Progression of simple fatty liver or steatosis to its severe form non-alcoholic steatohepatitis (NASH) and liver fibrosis has been explained by a 'two-hit hypothesis'. Whilst simple steatosis is considered the first hit, its transformation to NASH may be driven by a second hit. Of several factors that constitute the second hit, advanced glycation end products (AGEs), which are formed when reducing-sugars react with proteins or lipids, have been implicated as major candidates that drive steatosis to NASH via the receptor for AGEs (RAGE). Both endogenous and processed food-derived (exogenous) AGEs can activate RAGE, mainly present on Kupffer cells and hepatic stellate cells, thus propagating NAFLD progression. This review focuses on the pathophysiology of NAFLD with special emphasis on the role of food-derived AGEs in NAFLD progression to NASH and liver fibrosis. Moreover, the effect of dietary manipulation to reduce AGE content in food or the therapies targeting AGE/RAGE pathway on disease progression is also discussed.
机构:
Univ Innsbruck Hosp, Dept Med, Div Gastroenterol & Hepatol, AT-6020 Innsbruck, Austria
Christian Doppler Res Lab Gut Inflammat, Innsbruck, AustriaUniv Innsbruck Hosp, Dept Med, Div Gastroenterol & Hepatol, AT-6020 Innsbruck, Austria
机构:
Univ Sci & Technol, KIST Sch, Div Biomed Sci & Technol, Seoul 02792, South Korea
KIST Gangneung Inst Nat Prod, Nat Prod Informat Res Ctr, Kangnung 25451, South KoreaUniv Sci & Technol, KIST Sch, Div Biomed Sci & Technol, Seoul 02792, South Korea
Winarto, Jessica
Song, Dae-Geun
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Univ Sci & Technol, KIST Sch, Div Biomed Sci & Technol, Seoul 02792, South Korea
KIST Gangneung Inst Nat Prod, Nat Prod Informat Res Ctr, Kangnung 25451, South KoreaUniv Sci & Technol, KIST Sch, Div Biomed Sci & Technol, Seoul 02792, South Korea
Song, Dae-Geun
Pan, Cheol-Ho
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Univ Sci & Technol, KIST Sch, Div Biomed Sci & Technol, Seoul 02792, South Korea
KIST Gangneung Inst Nat Prod, Nat Prod Informat Res Ctr, Kangnung 25451, South Korea
Microalgae Ask US Co Ltd, Kangnung 25441, South KoreaUniv Sci & Technol, KIST Sch, Div Biomed Sci & Technol, Seoul 02792, South Korea