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标题:Enhanced AMPK phosphorylation contributes to the beneficial effects of Lactobacillus rhamnosus GG supernatant on chronic-alcohol-induced fatty liver disease
时间:2019-11-19 21:22:48
DOI:10.1016/j.jnutbio.2014.10.016
作者:Zhang, Min; Wang, Cuiling; Wang, Chunhong
关键词:Probiotics; Alcohol; Liver; Lipid; AMPK
出版源: The Journal of Nutritional Biochemistry ,26 (4) :337-344
摘要: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-a, peroxisome proliferator-activated receptor gamma coactivator protein-la and carnitine palmitoyltransferase-1, leading to increased fatty acid beta-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. (C) 2015 Elsevier Inc. All rights reserved.
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目录:
  • Enhanced AMPK phosphorylation contributes to the beneficial effects of Lactobacillus rhamnosus GG supernatant on chronic-al...
    • 1. Introduction
    • 2. Material and methods
      • 2.1. Culture of LGG
      • 2.2. Animal model
      • 2.3. Cell culture and treatment
      • 2.4. Biochemical assays
      • 2.5. Fatty liver assessment
      • 2.6. Liver apoptosis analysis
      • 2.7. Western blot analysis
      • 2.8. Quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR)
      • 2.9. Statistical analysis
    • 3. Results
      • 3.1. LGGs decreases chronic-alcohol-induced hepatic lipid accumulation and liver injury
      • 3.2. LGGs down-regulates SREBP-1 and up-regulates PPAR-α
      • 3.3. Effects of LGGs on hepatic AMPK signaling
      • 3.4. LGGs attenuates alcohol-induced hepatic apoptosis
    • 4. Discussion
    • Grants
    • Disclosures
    • Author contributions
    • Acknowledgements
    • References

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