المؤلفون: Julia Sauer, Agnes A. Steixner-Kumar, Svenja Gabler, Maciej Motyka, Jörg F. Rippmann, Stefan Brosa, Dennis Boettner, Tanja Schönberger, Charlotte Lempp, Vanessa Frodermann, Eric Simon, Oliver Krenkel, Ehsan Bahrami

المصدر: Frontiers in Immunology, Vol 15 (2024)

مصطلحات موضوعية: NASH - non-alcoholic steatohepatitis, inflammation, monocyte-derived macrophage (MDM), NK cells, liver fibrosis, Immunologic diseases. Allergy, RC581-607

الوصف: Chronic liver diseases, such as non-alcoholic steatohepatitis (NASH)-induced cirrhosis, are characterized by an increasing accumulation of stressed, damaged, or dying hepatocytes. Hepatocyte damage triggers the activation of resident immune cells, such as Kupffer cells (KC), as well as the recruitment of immune cells from the circulation toward areas of inflammation. After infiltration, monocytes differentiate into monocyte-derived macrophages (MoMF) which are functionally distinct from resident KC. We herein aim to compare the in vitro signatures of polarized macrophages and activated hepatic stellate cells (HSC) with ex vivo-derived disease signatures from human NASH. Furthermore, to shed more light on HSC activation and liver fibrosis progression, we investigate the effects of the secretome from primary human monocytes, macrophages, and NK cells on HSC activation. Interleukin (IL)-4 and IL-13 treatment induced transforming growth factor beta 1 (TGF-β1) secretion by macrophages. However, the supernatant transfer did not induce HSC activation. Interestingly, PMA-activated macrophages showed strong induction of the fibrosis response genes COL10A1 and CTGF, while the supernatant of IL-4/IL-13-treated monocytes induced the upregulation of COL3A1 in HSC. The supernatant of PMA-activated NK cells had the strongest effect on COL10A1 induction in HSC, while IL-15-stimulated NK cells reduced the expression of COL1A1 and CTGF. These data indicate that other factors, aside from the well-known cytokines and chemokines, might potentially be stronger contributors to the activation of HSCs and induction of a fibrotic response, indicating a more diverse and complex role of monocytes, macrophages, and NK cells in liver fibrosis progression.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1232070/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/8f49c0488c064420b392c7d96dc7899eTest

المؤلفون: Ali Nowroozi, Sara Momtazmanesh, Nima Rezaei

المصدر: Frontiers in Medicine, Vol 10 (2023)

مصطلحات موضوعية: COVID-19, MAFLD (metabolic associated fatty liver disease), NAFLD (non alcoholic fatty liver disease), NASH (non-alcoholic steatohepatitis), metabolic syndome, vaccine, Medicine (General), R5-920

الوصف: The COVID-19 pandemic is ongoing and places a substantial burden on healthcare systems worldwide. As we further shed light on different disease characteristics, we identify more and more groups of people at higher risk of poor COVID-19 outcomes. Metabolic-associated fatty liver disease (MAFLD) (previously non-alcoholic fatty liver disease or NAFLD) is a common metabolic disorder characterized by fat accumulation and liver fibrosis. Given its close correlation with metabolic syndrome, an established risk factor for severe COVID-19, it is necessary to investigate its interplay with the novel coronavirus. In this study, we review the available data on COVID-19 prognosis, treatment and prevention options in patients with MAFLD, and the effect that the disease and the pandemic have on MAFLD care. Furthermore, we point out the gaps in the current literature to accentuate the work that needs to be done to improve MAFLD care during the pandemic and beyond.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmed.2023.1126491/fullTest; https://doaj.org/toc/2296-858XTest

الوصول الحر: https://doaj.org/article/96136e8f5e7548f687506ef3b9a06d63Test

المؤلفون: Camille Pichon, Maxime Nachit, Justine Gillard, Greetje Vande Velde, Nicolas Lanthier, Isabelle A. Leclercq

المصدر: Frontiers in Nutrition, Vol 9 (2022)

مصطلحات موضوعية: MAFLD (metabolic-associated fatty liver disease), NASH (non-alcoholic steatohepatitis), ammonia, myosteatosis, L-ornithine L-aspartate, Nutrition. Foods and food supply, TX341-641

الوصف: BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in the world. Progression toward non-alcoholic steatohepatitis (NASH) is associated with alterations of skeletal muscle. One plausible mechanism for altered muscle compartment in liver disease is changes in ammonia metabolism. In the present study, we explored the hypothesis that NASH-associated hyperammonemia drives muscle changes as well as liver disease progression.Materials and methodsIn Alms1-mutant mice (foz/foz) fed a 60% fat diet (HFD) for 12 weeks; we investigated hepatic and muscular ammonia detoxification efficiency. We then tested the effect of an 8 week-long supplementation with L-ornithine L-aspartate (LOLA), a known ammonia-lowering treatment, given after either 4 or 12 weeks of HFD for a preventive or a curative intervention, respectively. We monitored body composition, liver and muscle state by micro computed tomography (micro-CT) as well as muscle strength by four-limb grip test.ResultsAccording to previous studies, 12 weeks of HFD induced NASH in all foz/foz mice. Increase of hepatic ammonia production and alterations of urea cycle efficiency were observed, leading to hyperammonemia. Concomitantly mice developed marked myosteatosis. First signs of myopenia occurred after 20 weeks of diet. Early LOLA treatment given during NASH development, but not its administration in a curative regimen, efficiently prevented myosteatosis and muscle quality, but barely impacted liver disease or, surprisingly, ammonia detoxification.ConclusionOur study confirms the perturbation of hepatic ammonia detoxification pathways in NASH. Results from the interventional experiments suggest a direct beneficial impact of LOLA on skeletal muscle during NASH development, though it does not improve ammonia metabolism or liver disease.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnut.2022.1051157/fullTest; https://doaj.org/toc/2296-861XTest

الوصول الحر: https://doaj.org/article/0e0e13ee4966406880ac31e13720af6dTest

المؤلفون: Constanze Hoebinger, Dragana Rajcic, Tim Hendrikx

المصدر: Frontiers in Cardiovascular Medicine, Vol 8 (2022)

مصطلحات موضوعية: NAFLD (non-alcoholic fatty liver disease), oxidized lipids, foamy macrophages, immunoglobulins, atherosclerosis, NASH (non-alcoholic steatohepatitis), Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: The prevalence of non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis to inflammatory steatohepatitis (NASH) and cirrhosis, continues to rise, making it one of the major chronic liver diseases and indications for liver transplantation worldwide. The pathological processes underlying NAFLD not only affect the liver but are also likely to have systemic effects. In fact, growing evidence indicates that patients with NAFLD are at increased risk for developing atherosclerosis. Indeed, cardiovascular complications are the leading cause of mortality in NAFLD patients. Here, we aim to address common pathophysiological molecular pathways involved in chronic fatty liver disease and atherosclerosis. In particular, we focus on the role of oxidized lipids and the formation of oxidation-specific epitopes, which are important targets of host immunity. Acting as metabolic danger signals, they drive pro-inflammatory processes and thus contribute to disease progression. Finally, we summarize encouraging studies indicating that oxidized lipids are promising immunological targets to improve intervention strategies for NAFLD and potentially limit the risk of developing atherosclerosis.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcvm.2021.824481/fullTest; https://doaj.org/toc/2297-055XTest

الوصول الحر: https://doaj.org/article/b2b1ec1ef1b547cd8ed253e7a4678c99Test

المؤلفون: Pichon, Camille, Nachit, Maxime, Gillard, Justine, Vande Velde, Greetje, Lanthier, Nicolas, Leclercq, Isabelle

المساهمون: UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service d'hépato-gastro-entérologie

المصدر: Frontiers in nutrition, Vol. 9, p. 1051157 [1-15] (2022)

مصطلحات موضوعية: L-ornithine L-aspartate, MAFLD (metabolic-associated fatty liver disease), NASH (non-alcoholic steatohepatitis), ammonia, myosteatosis

الوصف: BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in the world. Progression toward non-alcoholic steatohepatitis (NASH) is associated with alterations of skeletal muscle. One plausible mechanism for altered muscle compartment in liver disease is changes in ammonia metabolism. In the present study, we explored the hypothesis that NASH-associated hyperammonemia drives muscle changes as well as liver disease progression. MATERIALS AND METHODS: In Alms1-mutant mice (foz/foz) fed a 60% fat diet (HFD) for 12 weeks; we investigated hepatic and muscular ammonia detoxification efficiency. We then tested the effect of an 8 week-long supplementation with L-ornithine L-aspartate (LOLA), a known ammonia-lowering treatment, given after either 4 or 12 weeks of HFD for a preventive or a curative intervention, respectively. We monitored body composition, liver and muscle state by micro computed tomography (micro-CT) as well as muscle strength by four-limb grip test. RESULTS: According to previous studies, 12 weeks of HFD induced NASH in all foz/foz mice. Increase of hepatic ammonia production and alterations of urea cycle efficiency were observed, leading to hyperammonemia. Concomitantly mice developed marked myosteatosis. First signs of myopenia occurred after 20 weeks of diet. Early LOLA treatment given during NASH development, but not its administration in a curative regimen, efficiently prevented myosteatosis and muscle quality, but barely impacted liver disease or, surprisingly, ammonia detoxification. CONCLUSION: Our study confirms the perturbation of hepatic ammonia detoxification pathways in NASH. Results from the interventional experiments suggest a direct beneficial impact of LOLA on skeletal muscle during NASH development, though it does not improve ammonia metabolism or liver disease.

العلاقة: boreal:278451; http://hdl.handle.net/2078.1/278451Test; info:pmid/36466421; urn:EISSN:2296-861X

الإتاحة: https://doi.org/10.3389/fnut.2022.1051157Test
http://hdl.handle.net/2078.1/278451Test

المؤلفون: Hoebinger, C., Rajcic, D., Hendrikx, T.

المصدر: Hoebinger , C , Rajcic , D & Hendrikx , T 2022 , ' Oxidized Lipids: Common Immunogenic Drivers of Non-Alcoholic Fatty Liver Disease and Atherosclerosis ' , Frontiers in cardiovascular medicine , vol. 8 , 824481 . https://doi.org/10.3389/fcvm.2021.824481Test

مصطلحات موضوعية: NAFLD (non-alcoholic fatty liver disease), oxidized lipids, foamy macrophages, immunoglobulins, atherosclerosis, NASH (non-alcoholic steatohepatitis), OXIDATION-SPECIFIC EPITOPES, LOW-DENSITY-LIPOPROTEIN, MALONDIALDEHYDE EPITOPES, RECEPTOR 4, VITAMIN-E, B-CELLS, CAROTID ATHEROSCLEROSIS, REDUCES ATHEROSCLEROSIS, HEPATIC INFLAMMATION, STERILE INFLAMMATION

الوصف: The prevalence of non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis to inflammatory steatohepatitis (NASH) and cirrhosis, continues to rise, making it one of the major chronic liver diseases and indications for liver transplantation worldwide. The pathological processes underlying NAFLD not only affect the liver but are also likely to have systemic effects. In fact, growing evidence indicates that patients with NAFLD are at increased risk for developing atherosclerosis. Indeed, cardiovascular complications are the leading cause of mortality in NAFLD patients. Here, we aim to address common pathophysiological molecular pathways involved in chronic fatty liver disease and atherosclerosis. In particular, we focus on the role of oxidized lipids and the formation of oxidation-specific epitopes, which are important targets of host immunity. Acting as metabolic danger signals, they drive pro-inflammatory processes and thus contribute to disease progression. Finally, we summarize encouraging studies indicating that oxidized lipids are promising immunological targets to improve intervention strategies for NAFLD and potentially limit the risk of developing atherosclerosis.

الإتاحة: https://doi.org/10.3389/fcvm.2021.824481Test
https://cris.maastrichtuniversity.nl/en/publications/f66d03af-e8cf-49b0-93c6-2773948ef903Test

المؤلفون: Julia Sauer, Agnes A. Steixner-Kumar, Svenja Gabler, Maciej Motyka, Jörg F. Rippmann, Stefan Brosa, Dennis Boettner, Tanja Schönberger, Charlotte Lempp, Vanessa Frodermann, Eric Simon, Oliver Krenkel, Ehsan Bahrami

مصطلحات موضوعية: Immunology, Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies), Autoimmunity, Cellular Immunology, Humoural Immunology and Immunochemistry, Immunogenetics (incl. Genetic Immunology), Innate Immunity, Transplantation Immunology, Tumour Immunology, Immunology not elsewhere classified, Genetic Immunology, Animal Immunology, Veterinary Immunology, NASH - non-alcoholic steatohepatitis, inflammation, monocyte-derived macrophage (MDM), NK cells, liver fibrosis

الوصف: Chronic liver diseases, such as non-alcoholic steatohepatitis (NASH)-induced cirrhosis, are characterized by an increasing accumulation of stressed, damaged, or dying hepatocytes. Hepatocyte damage triggers the activation of resident immune cells, such as Kupffer cells (KC), as well as the recruitment of immune cells from the circulation toward areas of inflammation. After infiltration, monocytes differentiate into monocyte-derived macrophages (MoMF) which are functionally distinct from resident KC. We herein aim to compare the in vitro signatures of polarized macrophages and activated hepatic stellate cells (HSC) with ex vivo-derived disease signatures from human NASH. Furthermore, to shed more light on HSC activation and liver fibrosis progression, we investigate the effects of the secretome from primary human monocytes, macrophages, and NK cells on HSC activation. Interleukin (IL)-4 and IL-13 treatment induced transforming growth factor beta 1 (TGF-β1) secretion by macrophages. However, the supernatant transfer did not induce HSC activation. Interestingly, PMA-activated macrophages showed strong induction of the fibrosis response genes COL10A1 and CTGF, while the supernatant of IL-4/IL-13-treated monocytes induced the upregulation of COL3A1 in HSC. The supernatant of PMA-activated NK cells had the strongest effect on COL10A1 induction in HSC, while IL-15-stimulated NK cells reduced the expression of COL1A1 and CTGF. These data indicate that other factors, aside from the well-known cytokines and chemokines, might potentially be stronger contributors to the activation of HSCs and induction of a fibrotic response, indicating a more diverse and complex role of monocytes, macrophages, and NK cells in liver fibrosis progression.

العلاقة: https://figshare.com/articles/dataset/Table_1_Diverse_potential_of_secretome_from_natural_killer_cells_and_monocyte-derived_macrophages_in_activating_stellate_cells_xlsx/25530688Test

الإتاحة: https://doi.org/10.3389/fimmu.2024.1232070.s002Test
https://figshare.com/articles/dataset/Table_1_Diverse_potential_of_secretome_from_natural_killer_cells_and_monocyte-derived_macrophages_in_activating_stellate_cells_xlsx/25530688Test

المؤلفون: Umar Hayat, Ali A. Siddiqui, Hayrettin Okut, Saba Afroz, Syed Tasleem, Ahmed Haris

المصدر: Annals of Hepatology, Vol 20, Iss , Pp 100254- (2021)

مصطلحات موضوعية: NAFLD (non-alcoholic fatty liver disease), NASH (Non-alcoholic steatohepatitis), Confidence interval, Relative risk, Coffee, Caffeine, Specialties of internal medicine, RC581-951

الوصف: Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) is a widespread chronic liver disease. It is considered a multifactorial disorder that can progress to liver fibrosis and cause a worldwide public health concern. Coffee consumption may have a protective impact on NAFLD and liver fibrosis. However, the evidence from the previous studies is inconsistent. This meta-analysis summarizes available literature. Materials and methods: This study comprises two meta-analyses. The first meta-analysis summarizes the effect of coffee consumption on NAFLD in those who did or did not drink coffee. The second analysis compares the risk of liver fibrosis development between NAFLD patients who did or did not drink coffee. Pooled risk ratios (RR) and confidence intervals (CI) of observational studies were estimated. Results: Of the total collected 321 articles, 11 met our eligibility criteria to be included in the analysis. The risk of NAFLD among those who drank coffee compared to those who did not was significantly lower with a pooled RR value of 0.77 (95% CI 0.60–0.98). Moreover, we also found a significantly reduced risk of liver fibrosis in those who drink coffee than those who did not drink in the NAFLD patients with the relative risk (RR) of 0.68 (95% CI 0.68–0.79). Conclusions: Regular coffee consumption is significantly associated with a reduced risk of NAFLD. It is also significantly associated with decreased risk of liver fibrosis development in already diagnosed NAFLD patients. Although coffee consumption may be considered an essential preventive measure for NAFLD, this subject needs further epidemiological studies.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1665268120301691Test; https://doaj.org/toc/1665-2681Test

الوصول الحر: https://doaj.org/article/4a50b7e6795f4504a9ca9e3cbd5f5e8aTest

المؤلفون: Remmerie, Anneleen, Martens, Liesbet, Scott, Charlotte

المصدر: FRONTIERS IN ENDOCRINOLOGY ; ISSN: 1664-2392

مصطلحات موضوعية: Biology and Life Sciences, Medicine and Health Sciences, NONALCOHOLIC STEATOHEPATITIS, LOCAL PROLIFERATION, HEPATIC RECRUITMENT, ADIPOCYTE DEATH, SPI-C, CELLS, INFLAMMATION, DEPLETION, NICHE, POLARIZATION, macrophages, adipose tissue, non-alcoholic fatty liver disease (NAFLD), single-cell, heterogeneity, liver, NASH (non-alcoholic steatohepatitis)

الوصف: The increasing prevalence of obesity is accompanied by a rising incidence in metabolic syndrome and related pathologies such as non-alcoholic fatty liver disease. Macrophages are hypothesized to play central roles in these diseases, through their role as inflammatory mediators and as such are thought to be potential targets for future therapies. Recently, single cell technologies have revealed significant heterogeneity within the macrophage pool in both liver and adipose tissue in obesity. Thus current efforts are focused on dissecting this heterogeneity and understanding the distinct functions of the individual subsets. In this review, we discuss the current knowledge regarding macrophage heterogeneity, ontogeny and functions in the context of obese adipose tissue and fatty liver disease and attempt to align the distinct populations described to date.

وصف الملف: text/plain

العلاقة: https://biblio.ugent.be/publication/8672783Test; http://hdl.handle.net/1854/LU-8672783Test; http://dx.doi.org/10.3389/fendo.2020.00259Test; https://biblio.ugent.be/publication/8672783/file/8672784Test

الإتاحة: https://doi.org/10.3389/fendo.2020.00259Test
https://biblio.ugent.be/publication/8672783Test
http://hdl.handle.net/1854/LU-8672783Test
https://biblio.ugent.be/publication/8672783/file/8672784Test

المؤلفون: Adnan Said, Ahmed Akhter

المصدر: Annals of Hepatology, Vol 16, Iss 4, Pp 538-547 (2017)

مصطلحات موضوعية: NASH (Non Alcoholic Steatohepatitis), NAFLD (Non Alcoholic Fatty Liver Disease), Rosiglitazone, Pioglitazone, Metformin, Vitamin E, Specialties of internal medicine, RC581-951

الوصف: Background: Currently, there is no standardized treatment regimen for non-alcoholic steatohepatitis. Aim: We performed a meta-analysis of high quality randomized controlled trials that evaluated treatment response to metformin, thiazolidinediones (TZDs), and vitamin E in adult patients with non-alcoholic steatohepatitis. Outcome measures were improvement in liver histology, biochemical, and anthropometric measures. Material and methods: Nine trials met inclusion criteria (3 with TZD, 3 with Metformin, 2 with Vitamin E and 1 with both TZD and Vitamin E.). Results: With metformin, weighted liver histologic scores for steatosis, ballooning, and fibrosis did not demonstrate significant improvement and lobular inflammation worsened significantly (weighted mean increase 0.21, 95% CI 0.11 to 0.31, P < 0.0001). The liver histology score including steatosis (OR 3.51, 95% CI 2.14 to 5.78) and lobular inflammation (OR 2.65, 95% CI 1.69 to 4.15) improved with TZDs. Hepatic fibrosis (OR 1.58, 95% CI 0.98 to 2.54) and ballooning scores (OR 1.84, 95% CI 0.94 to 3.58) did not demonstrate significant improvement. With Vitamin E, weighted liver histologic scores for steatosis (weighted mean decrease -0.60, 95% CI -0.85 to -0.35, P < 0.0001), lobular inflammation (weighted mean decrease -0.40, 95% CI -0.61 to -0.20, P = 0.0001) and ballooning (weighted mean decrease -0.30, 95% CI -0.54 to -0.07, P = 0.01) demonstrated significant improvement compared to placebo. Fibrosis did not significantly change. Conclusion: In patients with NASH, TZDs and Vitamin E improve liver histologic scores but metformin does not. Insulin resistance also improves with both TZDs and metformin. Fibrosis does not improve with any of the agents.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1665268119310907Test; https://doaj.org/toc/1665-2681Test

الوصول الحر: https://doaj.org/article/0fdac0997d634ee8a712497ab987c0d7Test