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Lactobacillus rhamnosus GG supernatant prevents acute alcohol‐induced liver steatosis and injury through ER stress and autophagy‐mediated signaling pathways
Author(s) -
Zhang Lan,
Li Huimin,
Kong Xiaoxia,
Feng Wenke
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.680.13
Subject(s) - autophagy , steatosis , liver injury , atg5 , endocrinology , medicine , alcohol , lactobacillus rhamnosus , chemistry , biology , pharmacology , biochemistry , apoptosis , lactobacillus , fermentation
Acute alcohol exposure induces ER stress and autophagy in mouse liver, which protect alcohol‐induced cell death by removing damaged proteins and cellular compartments. We have previously demonstrated that Lactobacillus rhamnosus GG culture supernatant (LGGs) prevents acute alcohol‐induced hepatic steatosis and injury. The purpose of this study was to determine whether the protective effect of LGGs against acute alcohol‐induced liver injury through regulating autophagy and ER stress signaling pathways. C57BL/6 mice on standard chow diet were supplemented with supernatant from LGG culture (10 9 colony‐forming unit/mouse) for 5 days, and one dose of alcohol at 6 g/kg body weight was administered via gavage. Liver tissues and serum samples were collected 6 hours after alcohol administration. LGGs pretreatment significantly suppressed acute alcohol‐induced liver injury measured by serum activities of alanine aminotransferase (ALT) and asparagine aminotransferase (AST), and reduced liver steatosis assessed by triglyceride content and Oil red O staining of the liver tissues. Ethanol exposure increased LC‐3II/LC‐3I protein ratio suggesting an upregulated autophagy response, which was normalized by LGGs pretreatment. mRNA levels of molecules involved in autophagy formation and mitophagy regulation including beclin‐1, Atg7, Atg5 and p62 were significantly increased in alcohol‐treated mouse livers and suppressed by LGGs pretreatment. Alcohol‐induced ER stress is a trigger of autophagy regulation. Our studies also showed that LGGs pretreatment decreased acute alcohol‐induced hepatic GRP78 and CHOP expression, indicating a down‐regulation of ER stress by LGGs. Further studies showed that LGGs significantly reduced alcohol‐induced ROS levels assessed by DHE staining and Cyp2e1 and NRF2 protein levels in the liver samples. These results suggest that LGGs prevent the acute alcohol‐induced liver injury by preventing ROS production leading to a decreased ER stress and a normalization of hepatic autophagy response to acute ethanol exposure. The use of bacteria‐free LGG culture supernatant provides a novel strategy for prevention of acute alcohol‐induced liver injury (LZ and HL contributed equally to this study). Support or Funding Information NIH This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .