Min Zhang1, Cuiling Wang2, Chunhong Wang3, Haiyang Zhao4, Cuiqing Zhao5, Yongping Chen6, Yuhua Wang7, Craig McClain8, Wenke Feng9. 1. College of Food Science and Engineering, Jilin Agricultural University, Changchun, China; Department of Medicine, University of Louisville, Louisville, KY, USA; Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, USA; School of Pharmacy, and First Affiliate Hospital, Wenzhou Medical University, Wenzhou, China. 2. Department of Medicine, University of Louisville, Louisville, KY, USA; Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, USA; College of Life Sciences, Northwest University, Xi'an, China. 3. Department of Medicine, University of Louisville, Louisville, KY, USA; Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, USA; Second Affiliated Hospital, Jilin University, Changchun, China. 4. College of Food Science and Engineering, Jilin Agricultural University, Changchun, China; School of Pharmacy, and First Affiliate Hospital, Wenzhou Medical University, Wenzhou, China; School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, China. 5. College of Food Science and Engineering, Jilin Agricultural University, Changchun, China; Department of Medicine, University of Louisville, Louisville, KY, USA; Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, USA; School of Basic Medical Sciences, Jilin University, Changchun, China. 6. Department of Medicine, University of Louisville, Louisville, KY, USA. 7. College of Food Science and Engineering, Jilin Agricultural University, Changchun, China; Department of Medicine, University of Louisville, Louisville, KY, USA; Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, USA. Electronic address: yuhua-ww@163.com. 8. Department of Medicine, University of Louisville, Louisville, KY, USA; Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, USA; Robley Rex VA Medical Center, Louisville, KY, USA. 9. Department of Medicine, University of Louisville, Louisville, KY, USA; Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, USA. Electronic address: wenke.feng@louisville.edu.
Abstract
BACKGROUND: 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. METHODS: 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 10(9) CFU/day/mouse was given in the liquid diet. Hepatic steatosis, liver enzymes and hepatic apoptosis were analyzed. RESULTS: 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-α, peroxisome proliferator-activated receptor gamma coactivator protein-1α and carnitine palmitoyltransferase-1, leading to increased fatty acid β-oxidation. Importantly, chronic alcohol exposure decreased adenosine-monophosphate-activated protein kinase (AMPK) phosphorylation and increased acetyl-CoA carboxylase 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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 10(9) CFU/day/mouse was given in the liquid diet. Hepatic steatosis, liver enzymes and hepatic apoptosis were analyzed. RESULTS: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-α, peroxisome proliferator-activated receptor gamma coactivator protein-1α and carnitine palmitoyltransferase-1, leading to increased fatty acid β-oxidation. Importantly, chronic alcohol exposure decreased adenosine-monophosphate-activated protein kinase (AMPK) phosphorylation and increased acetyl-CoA carboxylase 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. CONCLUSIONS: 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.