Prolonged feeding with green tea polyphenols exacerbates cholesterol-induced fatty liver disease in mice

Abstract

This study investigated the potential deleterious impact of dietary supplementation with green tea extract (GTE) on the progression of fatty liver disease, in a mouse model of cholesterol-induced steatohepatitis that represents chronic liver injury. Male C57BL mice (n = 32, 8-wk-old) were fed for 6 wk with one of the following diets: normal control diet (ND, Con), Con + 1% w/w polyphenols from GTE (Con + GTE); high cholesterol diet, Con + 1% cholesterol + 0.5% cholate w/w (HCD); HCD + 1% green tea polyphenols w/w (HCD + GTE). Hepatic steatosis, oxidative, and inflammatory markers and bile acid synthesis pathways were measured. HCD supplementation resulted in hepatic steatosis and liver damage. In animals supplemented with the HCD + GTE an exacerbated hepatic steatosis, oxidative stress, and inflammatory response were observed compared to HCD supplemented animals. HCD + GTE supplementation elevated blood levels of liver enzymes and serum bile acids compared HCD-treated animals. HCD + GTE supplementation altered bile acid synthesisin thecholesterol clearance pathway, inducing a shift from the classically regulated CYP7A1 pathway to the alternative acidic pathway. Prolonged GTE supplementation dramatically increased hepatic oxidative stress, inflammation and liver injury, and altered the bile acid synthesis pathway in mice fed a HCD.