title: Enhanced AMPK phosphorylation contributes to the beneficial effects of Lactobacillus rhamnosus GG supernatant on chronic-alcohol-induced fatty liver disease.
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.
authors.affiliation: 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.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Medicine, University of Louisville, Louisville, KY, USA.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Craig
authors.initials: C
authors.lastname: McClain
authors.affiliation: 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.
authors.forename: Wenke
authors.initials: W
authors.lastname: Feng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000410:Alanine Transaminase / Q000097:blood; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D015536:Down-Regulation; D005235:Fatty Liver, Alcoholic / Q000382:microbiology* / Q000628:therapy*; D052201:Lacticaseibacillus rhamnosus / Q000737:chemistry*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D019936:Probiotics / Q000008:administration & dosage; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D017077:Culture Media, Conditioned; D047493:PPAR alpha; D047495:PPAR gamma; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051028:bcl-2-Associated X Protein; D013230:Stearoyl-CoA Desaturase; D002334:Carnitine O-Palmitoyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Alcohol; Lipid; Liver; Probiotics