scholarly journals Genome-wide analysis identified proteins associated with mitochondrial function and inflammation activation crucially regulating the pathogenesis of fatty liver disease

2021 ◽  
Author(s):  
Letian Zhang ◽  
Tingjun Liu ◽  
Chengzhang Hu ◽  
Xuan Zhang ◽  
Qin Zhang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Biological Processes ◽  
Human Beings ◽  
Alcoholic Fatty Liver ◽  
Therapeutic Drugs ◽  
Genome Wide ◽  
Performance Results

Abstract Background Fatty liver disease prevalently occurs in commercial postpartum dairies, resulting in a worldwide high culling rate because of their subsequent limitations of production and reproduction performance. Results Fatty liver-specific proteome and acetylome analysis revealed that energy metabolism suppression closely associated with mitochondrial dysfunction and inflammation activation are shown to be remarkable biological processes underlying the development of fatty liver disease, thereby acetylation modification of proteins modulating these processes. Twenty pivotal genetic factors/genes that differentially expressing and being acetylation modified in liver were identified and proposed to regulate the pathogenesis of fatty liver dairies. These proteins were confirmed to be differentially expressing in individual liver tissues, eight of which being validated through immunohistochemistry assay. Conclusion This study provided a comprehensive proteome and acetylome profile of fatty liver of dairy cows, and revealed potential important biological processes and essential regulators in the pathogenesis of fatty liver disease. Expectantly, understanding the molecular mechanisms of the pathogenesis of fatty liver disease in dairies, as an animal model of non-alcoholic fatty liver disease (NAFLD) in human beings, which is a clinico-pathologically defined process associated with metabolic syndrome, could inspire and facilitate the development of efficacious therapeutic drugs on NAFLD.

scholarly journals Proteome analysis identified proteins associated with mitochondrial function and inflammation activation crucially regulating the pathogenesis of fatty liver disease

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Letian Zhang ◽  
Tingjun Liu ◽  
Chengzhang Hu ◽  
Xuan Zhang ◽  
Qin Zhang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Proteome Analysis ◽  
Biological Processes ◽  
Human Beings ◽  
Alcoholic Fatty Liver ◽  
Therapeutic Drugs ◽  
Alcoholic Fatty Liver Disease

Abstract Background Fatty liver disease prevalently occurs in commercial postpartum dairies, resulting in a worldwide high culling rate because of their subsequent limitations of production and reproduction performance. Results Fatty liver-specific proteome and acetylome analysis revealed that energy metabolism suppression closely associated with mitochondrial dysfunction and inflammation activation were shown to be remarkable biological processes underlying the development of fatty liver disease, furthermore, acetylation modification of proteins could be one of the main means to modulate these processes. Twenty pivotal genetic factors/genes that differentially expressing and being acetylation modified in liver were identified and proposed to regulate the pathogenesis of fatty liver dairies. These proteins were confirmed to be differentially expressing in individual liver tissue, eight of which being validated via immunohistochemistry assay. Conclusions This study provided a comprehensive proteome and acetylome profile of fatty liver of dairy cows, and revealed potential important biological processes and essential regulators in the pathogenesis of fatty liver disease. Expectantly, understanding the molecular mechanisms of the pathogenesis of fatty liver disease in dairies, as an animal model of non-alcoholic fatty liver disease (NAFLD) in human beings, which is a clinico-pathologically defined process associated with metabolic syndrome, could inspire and facilitate the development of efficacious therapeutic drugs on NAFLD.

Molecular mechanisms of non-alcoholic fatty liver disease development

2021 ◽  
Vol 24 (4) ◽  
pp. 120
Author(s):  
T.S. Sall ◽  
E.S. Shcherbakova ◽  
S.I. Sitkin ◽  
T.Ya. Vakhitov ◽  
I.G. Bakulin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Disease Development ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Is liver fat detrimental to vessels?: intersections in the pathogenesis of NAFLD and atherosclerosis

2008 ◽  
Vol 115 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Paola Loria ◽  
Amedeo Lonardo ◽  
Giovanni Targher
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Liver Fat ◽  
Cvd Risk ◽  
Alcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Major Player

NAFLD (non-alcoholic fatty liver disease) encompasses the spectrum of fatty liver disease in insulin-resistant individuals who often display T2DM (Type 2 diabetes mellitus) and obesity. The present review highlights the pathophysiological basis and clinical evidence for a possible causal linkage between NAFLD and CVD (cardiovascular disease). The role of traditional and non-traditional CVD risk factors in the pathophysiology of NAFLD is considered in the first part of the review, with the basic science shared by atherogenesis and hepatic steatogenesis discussed in depth in the second part. In conclusion, NAFLD is not an innocent bystander, but a major player in the development and progression of CVD. NAFLD and CVD also share similar molecular mechanisms and targeted treatment strategies. On the research side, studies should focus on interventions aimed at restoring energy homoeostasis in lipotoxic tissues and at improving hepatic (micro)vascular blood supply.

scholarly journals A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression

2020 ◽  
Vol 9 (5) ◽  
pp. 1369 ◽  
Author(s):  
Paula Iruzubieta ◽  
Juan M. Medina ◽  
Raúl Fernández-López ◽  
Javier Crespo ◽  
Fernando de la Cruz
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Disease Progression ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Alcohol Fermentation ◽  
Alcoholic Fatty Liver ◽  
Liver Disease Progression ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.

scholarly journals Hepatokines and Non-Alcoholic Fatty Liver Disease: Linking Liver Pathophysiology to Metabolism

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1903
Author(s):  
Tae Hyun Kim ◽  
Dong-Gyun Hong ◽  
Yoon Mee Yang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Therapeutic Targets ◽  
Signaling Crosstalk ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The liver plays a key role in maintaining energy homeostasis by sensing and responding to changes in nutrient status under various metabolic conditions. Recently highlighted as a major endocrine organ, the contribution of the liver to systemic glucose and lipid metabolism is primarily attributed to signaling crosstalk between multiple organs via hepatic hormones, cytokines, and hepatokines. Hepatokines are hormone-like proteins secreted by hepatocytes, and a number of these have been associated with extra-hepatic metabolic regulation. Mounting evidence has revealed that the secretory profiles of hepatokines are significantly altered in non-alcoholic fatty liver disease (NAFLD), the most common hepatic manifestation, which frequently precedes other metabolic disorders, including insulin resistance and type 2 diabetes. Therefore, deciphering the mechanism of hepatokine-mediated inter-organ communication is essential for understanding the complex metabolic network between tissues, as well as for the identification of novel diagnostic and/or therapeutic targets in metabolic disease. In this review, we describe the hepatokine-driven inter-organ crosstalk in the context of liver pathophysiology, with a particular focus on NAFLD progression. Moreover, we summarize key hepatokines and their molecular mechanisms of metabolic control in non-hepatic tissues, discussing their potential as novel biomarkers and therapeutic targets in the treatment of metabolic diseases.

scholarly journals Hepatic Lipidomics and Molecular Imaging in a Murine Non-Alcoholic Fatty Liver Disease Model: Insights into Molecular Mechanisms

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1275
Author(s):  
Ricardo Rodríguez-Calvo ◽  
Sara Samino ◽  
Josefa Girona ◽  
Neus Martínez-Micaelo ◽  
Pere Ràfols ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Adipose Tissue ◽  
Liver Disease ◽  
Molecular Imaging ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Tissue Imaging ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

An imbalance between hepatic fatty acid uptake and removal results in ectopic fat accumulation, which leads to non-alcoholic fatty liver disease (NAFLD). The amount and type of accumulated triglycerides seem to play roles in NAFLD progression; however, a complete understanding of how triglycerides contribute to NAFLD evolution is lacking. Our aim was to evaluate triglyceride accumulation in NAFLD in a murine model and its associations with molecular mechanisms involved in liver damage and adipose tissue-liver cross talk by employing lipidomic and molecular imaging techniques. C57BL/6J mice fed a high-fat diet (HFD) for 12 weeks were used as a NAFLD model. Standard-diet (STD)-fed animals were used as controls. Standard liver pathology was assessed using conventional techniques. The liver lipidome was analyzed by liquid chromatography–mass spectrometry (LC–MS) and laser desorption/ionization–mass spectrometry (LDI–MS) tissue imaging. Liver triglycerides were identified by MS/MS. The transcriptome of genes involved in intracellular lipid metabolism and inflammation was assessed by RT-PCR. Plasma leptin, resistin, adiponectin, and FABP4 levels were determined using commercial kits. HFD-fed mice displayed increased liver lipid content. LC–MS analyses identified 14 triglyceride types that were upregulated in livers from HFD-fed animals. Among these 14 types, 10 were identified in liver cross sections by LDI–MS tissue imaging. The accumulation of these triglycerides was associated with the upregulation of lipogenesis and inflammatory genes and the downregulation of β-oxidation genes. Interestingly, the levels of plasma FABP4, but not of other adipokines, were positively associated with 8 of these triglycerides in HFD-fed mice but not in STD-fed mice. Our findings suggest a putative role of FABP4 in the liver-adipose tissue cross talk in NAFLD.

Integrated Bioinformatics Analysis Reveals Potential Mechanisms Associated with Intestinal Flora Intervention in Non-alcoholic Fatty Liver Disease

2020 ◽  
Author(s):  
Yingying Liu ◽  
Xinkui Liu ◽  
Wei Zhou ◽  
Jingyuan Zhang ◽  
Siyu Guo ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Intestinal Flora ◽  
Global Public Health ◽  
Alcoholic Fatty Liver ◽  
Key Genes ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease that imposes a huge economic burden on global public health. And the gut-liver axis theory supports the therapeutic role of intestinal flora in the development and progression of NAFLD. To this end, we designed bioinformatics study on the relationship between intestinal flora disorder and NAFLD, so as to explore the molecular mechanism of intestinal flora interfering with NAFLD. Methods Differentially expressed genes for NAFLD were obtained from GEO database. And the disease genes for NAFLD and intestinal flora disorder were obtained from the disease databases. Using string 11.0 database to establish protein-protein interaction network relationship and cytoscape 3.7.2 software visualization. Cytoscape plug-in MCODE and cytoHubba were used to screen the potential genes of intestinal flora disorder and NAFLD, so as to obtain potential targets for intestinal flora to interfere in the occurrence and process of NAFLD. Enrichment analysis of potential targets was carried out using R 4.0.2 software. Results The results showed that PTGS2, SPINK1 and C5AR1 may be the key genes for intestinal flora to interfere with NAFLD. CCL2, IL6, IL1B and FOS may be key genes for the development and progression of NAFLD. The gene function is mainly reflected in basic biological processes, including the regulation of metabolic process, epithelial development and immune influence. The pathway is mainly related to signal transduction, immune regulation and physiological metabolism. The TNF signaling pathway, AGE-RAGE signaling pathway in the diabetic activity, and NF-Kappa B signaling pathways are important pathways for intestinal flora to interfere with NAFLD. Conclusion According to the analysis results, there is a certain correlation between intestinal flora disorder and NAFLD. It is speculated that the mechanism by which intestinal flora may interfere with the occurrence and development of NAFLD is mainly related to inflammatory response and insulin resistance. Nevertheless, further research is needed to explore the specific molecular mechanisms.

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