Nonalcoholic steatohepatitis (NASH) is a common liver disease in which fat builds up in the liver without heavy alcohol use. Although obesity is correlated with an increased risk of NASH, it is not the decisive factor since NASH can be developed in lean people. Recent studies have suggested that inflammatory and metabolic disorders caused by the dysbiosis of gut microbiota potentially accelerate the progression of NASH, moreover, proinflammatory cytokines and oxidative stress are considered to play an important role in promoting hepatic inflammation, lipid peroxidation, and fibrosis. On the other hand, dietary polyphenols have been suggested to attenuate both oxidative stress and inflammation. In special, berries such as bilberry and haskap are polyphenol-rich dietary source and have been reported to possess anti-microbial, antioxidant, and anti-inflammatory activities. Based on the information of NASH and berry polyphenols, we investigated the protective effects and mechanisms of berry polyphenols on NASH, using a high fat and cholesterol diet-induced mouse NASH model. Our data revealed that berry polyphenols improved histopathological features of NASH with lower levels of lipid peroxidation and inflammatory cytokines. Molecular data further demonstrated that berry polyphenols upregulated the expression of Nrf2-mediated antioxidant enzymes, and improved FoxO1-mediated insulin-resistance in the liver of NASH mice. Moreover, the data from gut microbiome analyses revealed that berry polyphenols improved the status of gut microbiome by reducing the ratio of Firmicutes / Bacteroidetes, and enhancing the population of Akkermansia stain. In summary, our data demonstrated that dietary supplementation of berry polyphenols is able to prevent the high fat and cholesterol diet-induced NASH in mouse model by improving gut microbiome, and ameliorating inflammation as well as lipid peroxidation.

Preventive effects and molecular mechanisms of berry polyphenols in experimental nonalcoholic steatohepatitis (NASH)

256th National Meeting (2018)

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