Endogenous ethanol produced by intestinal bacteria induces mitochondrial dysfunction in non‐alcoholic fatty liver disease

2020 ◽  
Vol 35 (11) ◽  
pp. 2009-2019 ◽  
Author(s):  
Xiao Chen ◽  
Zheng Zhang ◽  
Huan Li ◽  
Jiangtao Zhao ◽  
Xiao Wei ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Mitochondrial Dysfunction ◽  
Fatty Liver Disease ◽  
Intestinal Bacteria ◽  
Alcoholic Fatty Liver ◽  
Endogenous Ethanol ◽  
Alcoholic Fatty Liver Disease

Mitochondrial dysfunction in non-alcoholic fatty liver disease and insulin resistance: Cause or consequence?

2013 ◽  
Vol 47 (11) ◽  
pp. 854-868 ◽  
Author(s):  
C. García-Ruiz ◽  
A. Baulies ◽  
M. Mari ◽  
P. M. García-Rovés ◽  
J. C. Fernandez-Checa
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Mitochondrial Dysfunction ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Integration of Multi-omics Data from Mouse Diversity Panel Highlights Mitochondrial Dysfunction in Non-alcoholic Fatty Liver Disease

Cell Systems ◽  
2018 ◽  
Vol 6 (1) ◽  
pp. 103-115.e7 ◽  
Author(s):  
Karthickeyan Chella Krishnan ◽  
Zeyneb Kurt ◽  
Rio Barrere-Cain ◽  
Simon Sabir ◽  
Aditi Das ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Mitochondrial Dysfunction ◽  
Fatty Liver Disease ◽  
Omics Data ◽  
Alcoholic Fatty Liver ◽  
Diversity Panel ◽  
Alcoholic Fatty Liver Disease

scholarly journals Exposure to Plasma From Non-alcoholic Fatty Liver Disease Patients Affects Hepatocyte Viability, Generates Mitochondrial Dysfunction, and Modulates Pathways Involved in Fat Accumulation and Inflammation

2021 ◽  
Vol 8 ◽  
Author(s):  
Elena Grossini ◽  
Divya Praveen Garhwal ◽  
Giuseppe Calamita ◽  
Raffaele Romito ◽  
Cristina Rigamonti ◽  
...  
Keyword(s):  
Liver Disease ◽  
Membrane Potential ◽  
Fatty Liver ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Membrane Potential ◽  
Nlrp3 Inflammasome ◽  
Fatty Liver Disease ◽  
Mitochondrial Membrane ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Changes of lipidic storage, oxidative stress and mitochondrial dysfunction may be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Although the knowledge of intracellular pathways has vastly expanded in recent years, the role and mechanisms of circulating triggering factor(s) are debated. Thus, we tested the hypothesis that factors circulating in the blood of NAFLD patients may influence processes underlying the disease. Huh7.5 cells/primary human hepatocytes were exposed to plasma from 12 NAFLD patients and 12 healthy subjects and specific assays were performed to examine viability, H2O2 and mitochondrial reactive oxygen species (ROS) release, mitochondrial membrane potential and triglycerides content. The involvement of NLRP3 inflammasome and of signaling related to peroxisome-proliferator-activating-ligand-receptor-γ (PPARγ), sterol-regulatory-element-binding-protein-1c (SREBP-1c), nuclear-factor-kappa-light-chain-enhancer of activated B cells (NF-kB), and NADPH oxidase 2 (NOX2) was evaluated by repeating the experiments in the presence of NLRP3 inflammasome blocker, MCC950, and through Western blot. The results obtained shown that plasma of NAFLD patients was able to reduce cell viability and mitochondrial membrane potential by about 48 and 24% (p < 0.05), and to increase H2O2, mitochondrial ROS, and triglycerides content by about 42, 19, and 16% (p < 0.05), respectively. An increased expression of SREBP-1c, PPARγ, NF-kB and NOX2 of about 51, 121, 63, and 46%, respectively, was observed (p < 0.05), as well. Those effects were reduced by the use of MCC950. Thus, in hepatocytes, exposure to plasma from NAFLD patients induces a NAFLD-like phenotype by interference with NLRP3-inflammasome pathways and the activation of intracellular signaling related to SREBP-1c, PPARγ, NF-kB and NOX2.

scholarly journals Klebsiella pneumonia, one of potential chief culprits of non-alcoholic fatty liver disease: through generation of endogenous ethanol

2018 ◽  
Author(s):  
Xiao Wei ◽  
Xiangna Zhao ◽  
Chen Chen ◽  
Jing Lu ◽  
Weiwei Cheng ◽  
...  
Keyword(s):  
Liver Disease ◽  
Klebsiella Pneumoniae ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Expression Profiles ◽  
Klebsiella Pneumonia ◽  
High Alcohol ◽  
Alcoholic Fatty Liver ◽  
Endogenous Ethanol ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD), a prelude of cirrhosis and hepatocellular carcinoma, is the most common chronic liver disease worldwide. NAFLD has been considerated to be associated with the composition of gut microbiota. However, causal relationship between change of gut microbiome and NAFLD remains unclear. Here we show that Klebsiella pneumoniae was significantly associated with NAFLD through inducing generation of endogenous ethanol. A strain of high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) was initially isolated from fecal samples of patient with non-alcoholic steatohepatitis (NASH) accompanied with auto-brewery syndrome (ABS). Gavage of HiAlc Kpn was capable of inducing murine model of fatty liver disease (FLD) in which had typical pathological changes of hepatic steatosis and similar liver gene expression profiles to those of alcohol intake in mice. Data derived from germ-free mice by gnotobiotic gavage further demonstrated that the HiAlc Kpn is the major cause of the changes in FLD mice. Furthermore, using proteomic and metabolitic analysis, we found that HiAlc Kpn induced generation of endogenous alcohol through the 2,3-butanediol fermentation pathway. More interestingly, the blood alcohol concentration was elevated in FLD mice induced by HiAlc Kpn after glucose intake. Clinical analysis showed that HiAlc Kpn were observed in up to 60% of patients with NAFLD. Our results suggested that HiAlc Kpn make important contribution to NAFLD, possibly through generation of the endogenous alcohol. Thus, targeting these bacteria might provide a novel therapeutic for clinical treatment of NAFLD.In BriefFatty liver disease induced by high alcohol-producing Klebsiella pneumoniaeCompeting Financial Interest StatementThe authors declare no conflicts of interest.

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