scholarly journals Extracellular Vesicles as Drivers of Non-Alcoholic Fatty Liver Disease: Small Particles with Big Impact

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 93
Author(s):  
David Højland Ipsen ◽  
Pernille Tveden-Nyborg

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading chronic liver disease, negatively affecting the lives of millions of patients worldwide. The complex pathogenesis involves crosstalk between multiple cellular networks, but how the intricate communication between these cells drives disease progression remains to be further elucidated. Furthermore, the disease is not limited to the liver and includes the reprogramming of distant cell populations in different organs. Extracellular vesicles (EVs) have gained increased attention as mediators of cellular communication. EVs carry specific cargos that can act as disease-specific signals both locally and systemically. Focusing on NAFLD advancing to steatohepatitis (NASH), this review provides an update on current experimental and clinical findings of the potential role of EVs in hepatic inflammation and fibrosis, the main contributors to progressive NASH. Particular attention is placed on the characteristics of EV cargos and potential specificity to disease stages, with putative value as disease markers and treatment targets for future investigations.

2020 ◽  
Vol 20 (7) ◽  
pp. 578-583
Author(s):  
Hui Li ◽  
Erna Jia ◽  
Yu Hong ◽  
Yanzhen Chen ◽  
Jian Jiao

Nonalcoholic Fatty Liver Disease (NAFLD) includes a variety of changes including nonalcoholic fatty liver, cirrhosis and Hepatocellular Carcinoma (HCC), which are associated with metabolic disorders and cardiovascular diseases. The pathogenesis of NAFLD is complex and multifactorial. Many studies have shown that estrogen has a protective effect on premenopausal women with metabolic disorders and non-alcoholic fatty liver disease. Estrogen supplements may, at least in theory, prevent the development and progression of NAFLD. Phytoestrogen is extracted from plants, especially legumes, whose molecular structure and biological activity are similar to those of mammals estrogen, therefore it could replace the role of estrogen and prevent the occurrence of adverse reactions to estrogen. In this article, we review the published literature related to phytoestrogens and NAFLD as well as suggest the possible mechanisms that may underlie the association between phytoestrogens and NAFLD.


Author(s):  
Мария Владимировна Абрамян ◽  
Алина Викторовна Свиридова ◽  
Елена Николаевна Веселова

Велика ли роль инфекции Helicobacter pylori на патогенез неалкогольной жировой болезни печени (НАЖБП)? Последние данные свидетельствуют о наличии их взаимосвязи [1, 2]. Однако до сих пор данная тема остается под вопросом. Цель данной работы - исследовать возможную связь и клиническое значение Helicobacter pylori в патогенезе неалкогольной жировой болезни печени. Is the role of Helicobacter pylori infection on the pathogenesis of non-alcoholic fatty liver disease (NAFLD) significant? Recent data indicate the presence of their relationship [1, 2]. However, until now, this topic remains in question. The aim of this work is to investigate the possible relationship and clinical significance of Helicobacter pylori in the pathogenesis of non-alcoholic fatty liver disease


Author(s):  
Alexandre Villard ◽  
Jérôme Boursier ◽  
Ramaroson Andriantsitohaina

The liver and intestine communicate in a bi-directional way through the biliary tract, portal vein, and other components of the gut-liver axis. The gut microbiota is one of the major contributors to the production of several proteins and bile acids. Imbalance in the gut bacterial community, called dysbiosis, participates in the development and progression of several chronic liver diseases, such as non-alcoholic fatty liver disease (NAFLD). NAFLD is currently considered the main chronic liver disease worldwide. Dysbiosis contributes to NAFLD development and progression, notably by a greater translocation of pathogen-associated molecular patterns (PAMPs) in the blood. Lipopolysaccharide (LPS) is a PAMP that activates toll-like receptor 4 (TLR4), induces liver inflammation, and participates in the development of fibrogenesis. LPS can be transported by bacterial extracellular vesicles (EVs). EVs are spherical structures produced by eukaryotic and prokaryotic cells that transfer information to distant cells and may represent new players in NAFLD development and progression. The present review summarizes the role of eukaryotic EVs, either circulating or tissue-derived, in NAFLD features, such as liver inflammation, angiogenesis, and fibrosis. Circulating EV levels are dynamic and correlate with disease stage and severity. However, scarce information is available concerning the involvement of bacterial EVs in liver disease. The present review highlights a potential role of bacterial EVs in insulin resistance and liver inflammation, although the mechanism involved has not been elucidated. Additionally, because of their distinct signatures, eukaryotic and prokaryotic EVs may also represent a promising NAFLD diagnostic tool as a "liquid biopsy" in the future.


2019 ◽  
Vol 91 (2) ◽  
pp. 143-148 ◽  
Author(s):  
V A Akhmedov ◽  
O V Gaus

The article provides an overview of modern views on the role of intestinal microbiota in the formation of non-alcoholic fatty liver disease. The general questions of the pathogenesis of the syndrome of excessive bacterial growth in the intestine, the participation of opportunistic microflora, the deficit of representatives of normal microflora, changes in the species composition of bile acids in the pathogenesis of nonalcoholic fatty liver disease are considered.


2018 ◽  
Vol 1 (2) ◽  
pp. 24-28
Author(s):  
Tanita Suttichaimongkol

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of death from liver cirrhosis, endstage liver disease, and hepatocellular carcinoma. It is also associated with increased cardiovasculardisease and cancer related mortality. While lifestyle modifications are the mainstay of treatment,only a proportion of patients are able to make due to difficult to achieve and maintain, and so moretreatment options are required such as pharmacotherapy. This review presents the drugs used inmanaging NAFLD and their pharmacologic targets. Therapies are currently directed towards improvingthe metabolic status of the liver, insulin resistance, cell oxidative stress, apoptosis, inflammation orfibrosis. Several agents are now in large clinical trials and within the next few years, the availability oftherapeutic options for NAFLD will be approved.     Keywords: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, fibrosis, cirrhosis  


2021 ◽  
Vol 10 (5) ◽  
pp. 1081
Author(s):  
Mikkel Parsberg Werge ◽  
Adrian McCann ◽  
Elisabeth Douglas Galsgaard ◽  
Dorte Holst ◽  
Anne Bugge ◽  
...  

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing and approximately 25% of the global population may have NAFLD. NAFLD is associated with obesity and metabolic syndrome, but its pathophysiology is complex and only partly understood. The transsulfuration pathway (TSP) is a metabolic pathway regulating homocysteine and cysteine metabolism and is vital in controlling sulfur balance in the organism. Precise control of this pathway is critical for maintenance of optimal cellular function. The TSP is closely linked to other pathways such as the folate and methionine cycles, hydrogen sulfide (H2S) and glutathione (GSH) production. Impaired activity of the TSP will cause an increase in homocysteine and a decrease in cysteine levels. Homocysteine will also be increased due to impairment of the folate and methionine cycles. The key enzymes of the TSP, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), are highly expressed in the liver and deficient CBS and CSE expression causes hepatic steatosis, inflammation, and fibrosis in animal models. A causative link between the TSP and NAFLD has not been established. However, dysfunctions in the TSP and related pathways, in terms of enzyme expression and the plasma levels of the metabolites (e.g., homocysteine, cystathionine, and cysteine), have been reported in NAFLD and liver cirrhosis in both animal models and humans. Further investigation of the TSP in relation to NAFLD may reveal mechanisms involved in the development and progression of NAFLD.


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 687
Author(s):  
Daniela Gabbia ◽  
Luana Cannella ◽  
Sara De De Martin

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.


2017 ◽  
Vol 23 (10) ◽  
pp. 1881 ◽  
Author(s):  
Shira Zelber-Sagi ◽  
Shiran Bord ◽  
Gali Dror-Lavi ◽  
Matthew Lee Smith ◽  
Samuel D Towne Jr ◽  
...  

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