Research Article Details
| Article ID: | A47118 |
| PMID: | 25622859 |
| Source: | J Nutr Biochem |
| 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. |
| DOI: | 10.1016/j.jnutbio.2014.10.016 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T01 | 5'-AMP-activated protein kinase subunit beta-1 | PRKAB1 | activator | Kinase | Q9Y478 | AAKB1_HUMAN | Details |
| T05 | Peroxisome proliferator-activated receptor gamma | PPARG | agonist | Nuclear hormone receptor | P37231 | PPARG_HUMAN | Details |
| T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T22 | Stearoyl-CoA desaturase | SCD | inhibitor | Enzyme | O00767 | SCD_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D201 | L-Carnitine | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D284 | Probiotic | Supplement | -- | -- | -- | Under clinical trials | Details |
| D062 | Carnitine complex | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |