Elevation of liver endoplasmic reticulum stress in a modified choline-deficient l -amino acid-defined diet-fed non-alcoholic steatohepatitis mouse model

Muraki, Yo; Makita, Yukimasa; Yamasaki, Midori; Amano, Yuichiro; Matsuo, Taisuke

doi:10.1016/j.bbrc.2017.03.072

Cited by 8 publications

(6 citation statements)

References 23 publications

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“…Accordingly, previous research has shown that restoration of autophagic flux in cardiomyocytes by activating the AMPK pathway reduced MIRI [39]. Another study also demonstrated that autophagy was enhanced in H9C2s following AMPK/mTOR activation and had protective effects on cells during hypoxia/reoxygenation injury [40].…”

Section: Discussionmentioning

confidence: 96%

Exosomes Derived from Mesenchymal Stem Cells Rescue Myocardial Ischaemia/Reperfusion Injury by Inducing Cardiomyocyte Autophagy Via AMPK and Akt Pathways

Liu

Jin

et al. 2017

Cell Physiol Biochem

271

184

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Background/Aims: Reperfusion after an ischaemic insult might cause infarct extension. Mesenchymal stem cell (MSC)-derived exosomes could attenuate myocardial remodelling in animal models of myocardial ischaemia reperfusion injury (MIRI), and the present study aimed to explore the related mechanisms. Methods: In vitro, rat H9C2 cardiomyocytes (H9C2s) were exposed to H₂O₂. Cell viability was detected by the CCK-8 assay, apoptosis was detected by Annexin V-PE/7-AAD staining, ROS production was detected by fluorescence microscopy and flow cytometry, and apoptosis-related proteins and signalling pathway-related proteins were detected by western blot analysis. Autophagic flux was measured using the tandem fluorescent mRFG-GFP-LC3 assay. MSC-derived exosomes were extracted using the total exosome isolation reagent. Apoptosis, myocardial infarction size, heart function and myocardial LC3B expression were examined in an in vivo I/R model by the TUNEL assay, TTC/Evan blue staining, echocardiography and immunohistochemicalstaining, respectively. Results: In vitro, H₂O₂ dose-dependently increased ROS production and cell apoptosis in H9C2s and blocked autophagic flux after 3 h of exposure; autophagy gradually decreased thereafter, and the lowest level was detected at 12 h after exposure. MSC-derived exosomes reduced H₂O₂-induced ROS production and cell apoptosis and enhanced autophagy at 12 h after exposure. In H9C2 cells exposed to H₂O₂ for 12 h, treatment with exosomes enhanced autophagy via the AMPK/mTOR and Akt/mTOR pathways. Likewise, in vivo exosome injections in rats that underwent I/R injury significantly reduced apoptosis and the myocardial infarct size and upregulated myocardial LC3B expression as well as improved heart function. Conclusions: Our results indicate that MSC-derived exosomes could reduce MIRI by inducing cardiomyocyte autophagy via AMPK/mTOR and Akt/mTOR pathways.

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Section: Discussionmentioning

confidence: 96%

Exosomes Derived from Mesenchymal Stem Cells Rescue Myocardial Ischaemia/Reperfusion Injury by Inducing Cardiomyocyte Autophagy Via AMPK and Akt Pathways

Liu

Jin

et al. 2017

Cell Physiol Biochem

271

184

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“…The excessive hepatic FFA influx in T2D patients, such as palmitic acid, cholesterol, lysophosphatidylcholine, and ceramides, directly causes lipotoxicity and induces liver inflammation and fibrosis (Tomita et al, 2014; Marra and Svegliati-Baroni, 2018). The oxidation and metabolism of excessive FFAs in the liver further cause oxidative stress (Paradies et al, 2014) and endoplasmic reticulum (ER) stress (Muraki et al, 2017) that trigger hepatocellular damage and apoptosis. In addition, excessive FFAs in the liver, the release of inflammatory mediators from dysfunctional adipose tissue (such as MCP-1, IL-6, and TNFα) (DI Maira et al, 2018), and endotoxins derived from gut (Carnevale et al, 2017) in diabetic patients with NAFLD also activate hepatic Kupffer cells (Kazankov et al, 2019) and release liver inflammatory mediators (IL-1β, TNFα, IL-6) to promote liver injury and inflammation (Yu et al, 2019).…”

Section: T2d Increases the Risk Of Nafld Progression To Nash Cirrhosmentioning

confidence: 99%

NAFLD and Diabetes: Two Sides of the Same Coin? Rationale for Gene-Based Personalized NAFLD Treatment

2019

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The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly and at the forefront of worldwide concern. Characterized by excessive fat accumulation in the liver, NAFLD regularly coexists with metabolic disorders, including type 2 diabetes, obesity, and cardiovascular disease. It has been well established that the presence of NAFLD increases the incidence of type 2 diabetes, while diabetes aggravates NAFLD to more severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, recent progress on the genotype/phenotype relationships in NAFLD patients indicates the development of NAFLD with a relative conservation of glucose metabolism in individuals with specific gene variants, such as the patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 protein (TM6SF2) variants. This review will focus on the clinical and pathophysiological connections between NAFLD and type 2 diabetes and will also discuss a disproportionate progression of NAFLD and diabetes, and the different responses to lifestyle and drug intervention in NAFLD patients with specific gene variants that may give insight into personalized treatment for NAFLD.

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“…Choline is an essential nutrient, which is important for cell structure and neurotransmitter synthesis [ 147 ]. Mice feed a choline-deficient diet for 4 weeks can induce a NASH-like syndrome and thus be used to model human NASH [ 148 , 149 ]. Choline deficiency has also been correlated with fatty liver in human studies [ 33 , 108 ].…”

Section: Mechanism Of Action Of Microbiome In Liver Disease Pathogenesis and Developmentmentioning

confidence: 99%

Human Gut Microbiome and Liver Diseases: From Correlation to Causation

Mao

et al. 2021

Microorganisms

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The important role of human gut microbiota in liver diseases has long been recognized as dysbiosis and the translocation of certain microbes from the gut to liver. With the development of high-throughput DNA sequencing, the complexity and integrity of the gut microbiome in the whole spectrum of liver diseases is emerging. Specific patterns of gut microbiota have been identified in liver diseases with different causes, including alcoholic, non-alcoholic, and virus induced liver diseases, or even at different stages, ranging from steatohepatitis, fibrosis, cirrhosis, to hepatocellular carcinoma. At the same time, the mechanism of how microbiota contributes to liver diseases goes beyond the traditional function of the gut–liver axis which could lead to liver injury and inflammation. With the application of proteomics, metabolomics, and modern molecular technologies, more microbial metabolites and the complicated interaction of microbiota with host immunity come into our understanding in the liver pathogenesis. Germ-free animal models serve as a workhorse to test the function of microbiota and their derivatives in liver disease models. Here, we review the current evidence on the relationship between gut microbiota and liver diseases, and the mechanisms underlying this phenotype. In addition to original liver diseases, gut microbiota might also affect liver injury in systemic disorders involving multiple organs, as in the case of COVID-19 at a severe state. A better understanding of the gut microbial contribution to liver diseases might help us better benefit from this guest–host relationship and pave the way for novel therapies.

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Elevation of liver endoplasmic reticulum stress in a modified choline-deficient l -amino acid-defined diet-fed non-alcoholic steatohepatitis mouse model

Cited by 8 publications

References 23 publications

Exosomes Derived from Mesenchymal Stem Cells Rescue Myocardial Ischaemia/Reperfusion Injury by Inducing Cardiomyocyte Autophagy Via AMPK and Akt Pathways

Exosomes Derived from Mesenchymal Stem Cells Rescue Myocardial Ischaemia/Reperfusion Injury by Inducing Cardiomyocyte Autophagy Via AMPK and Akt Pathways

NAFLD and Diabetes: Two Sides of the Same Coin? Rationale for Gene-Based Personalized NAFLD Treatment

Human Gut Microbiome and Liver Diseases: From Correlation to Causation

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