Enhanced AMPK phosphorylation contributes to the beneficial effects of Lactobacillus rhamnosus GG supernatant on chronic-alcohol-induced fatty liver disease.

Enhanced AMPK phosphorylation contributes to the beneficial effects of Lactobacillus rhamnosus GG supernatant on chronic-alcohol-induced fatty liver disease.
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DOI:
10.1016/j.jnutbio.2014.10.016
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发表时间:
2015-04
期刊:
The Journal of nutritional biochemistry
影响因子:
--
通讯作者:
Feng W
Feng W
中科院分区:
其他
文献类型:
--
作者:
Zhang M;Wang C;Wang C;Zhao H;Zhao C;Chen Y;Wang Y;McClain C;Feng W

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We have previously demonstrated that Lactobacillus rhamnosus GG culture supernatant (LGGs) prevents acute alcohol exposure-induced hepatic steatosis and injury. The protective effects of LGGs were attributed to the improved intestinal barrier function leading to decreased endotoxemia. The purpose of this study was to determine whether LGGs was effective in protecting against chronic alcohol-induced hepatic steatosis and injury, and to evaluate the underlying mechanisms of LGGs on hepatic lipid metabolism. C57BL/6N mice were fed liquid diet containing 5% alcohol or pair-fed isocaloric maltose dextrin for 4 weeks. LGGs at a dose equivalent to 109 CFU/day/mouse was given in the liquid diet. Hepatic steatosis, liver enzymes and hepatic apoptosis were analyzed. LGGs prevented alcohol-mediated increase in hepatic expression of lipogenic genes, sterol regulatory element binding protein-1 and Stearoyl-CoA desaturase-1 ; and increased the expression of peroxisome proliferator activated receptor-a, peroxisome proliferator-activated receptor gamma coactivator protein-1 α and carnitine palmitoyltransferase-1 leading to increased fatty acid β-oxidation. Importantly, chronic alcohol exposure decreased AMPK phosphorylation and increased acetyl-CoA carboxylase (ACC) activity, which were attenuated by LGGs administration. LGGs also decreased Bax expression and increased Bcl-2 expression, which attenuated alcohol-induced hepatic apoptosis. These LGGs regulated molecular changes resulted in the attenuation of chronic alcohol exposure-mediated increase in hepatic fat accumulation and liver injury. Probiotic LGG culture supernatant is effective in the prevention of chronic alcohol exposure-induced hepatic steatosis and injury. LGGs likely exerts its beneficial effects, at least in part, through modulation of hepatic AMPK activation and Bax/Bcl-2-mediated apoptosis.
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