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 A Review of FoxO1-Regulated Metabolic Diseases and Related Drug Discoveries

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 184 ◽  
Author(s):  
Shiming Peng ◽  
Wei Li ◽  
Nannan Hou ◽  
Niu Huang
Keyword(s):  
Transcription Factor ◽  
Liver Disease ◽  
Energy Metabolism ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Regulation ◽  
Metabolic Diseases ◽  
Alcoholic Fatty Liver ◽  
Related Drug ◽  
Alcoholic Fatty Liver Disease

FoxO1 is a conserved transcription factor involved in energy metabolism. It is tightly regulated by modifications on its mRNA and protein and responds to environmental nutrient signals. FoxO1 controls the transcription of downstream genes mediating metabolic regulation. Dysfunction of FoxO1 pathways results in several metabolic diseases, including diabetes, obesity, non-alcoholic fatty liver disease, and atherosclerosis. Here, we summarize the mechanism of FoxO1 regulation behind these diseases and FoxO1-related drug discoveries.

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

scholarly journals Non-alcoholic fatty liver disease: current aspects of diagnosis in real clinical practice

2021 ◽  
Vol 2 (4) ◽  
pp. 40-50
Author(s):  
Dmitry I. Trukhan ◽  
Keyword(s):  
Clinical Practice ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Diagnostic Algorithm ◽  
Malignant Neoplasms ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease ◽  
Real Clinical Practice

In the diagnosis and subsequent supervision of patients with non-alcoholic fatty liver disease (NAFLD) and obesity in real clinical practice, the role and importance of the doctor of first contact (therapist and general practitioner) increases. Non-alcoholic fatty liver disease is currently considered as the hepatic component of metabolic syndrome. A diagnostic algorithm for NAFLD at the stage of primary health care is presented. The most difficult question at 2–4 levels of the diagnostic algorithm is the differential diagnosis between NAFLD and alcoholic liver disease. During a pandemic of a novel coronavirus infection (COVID-19), patients with NAFLD or NASH, as a rule, have concomitant metabolic diseases such as diabetes mellitus, arterial hypertension and obesity, and also have to take a large number of potentially hepatotoxic drugs, it is advisable to classify them as elevated risk of infection with SARS-CoV-2, and the severe course of this infection. This allows us to consider NAFLD as dangerous in terms of the severe course of COVID-19, as viral hepatitis, autoimmune hepatitis and liver fibrosis / cirrhosis. It is known that NAFLD is an independent predictor of not only high cardiovascular risks, but also hepatocellular carcinoma and malignant neoplasms of various localization, as well as a number of other comorbid conditions. The review concludes with a clinical observation illustrating the difficulty of early diagnosis of intrahepatic cholangiocarcinoma in a patient with NAFLD and other metabolic risk factors.

scholarly journals NON-ALCOHOLIC FATTY LIVER DISEASE IN THE CONTEXT OF ALTERED GUT MICROBIOTA

2021 ◽  
Vol 74 (4) ◽  
pp. 1007-1010
Author(s):  
Tetyana V. Koval ◽  
Ivan V. Chopey ◽  
Mykhaylo M. Hechko ◽  
Artur V. Kurakh
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Intestinal Microbiome ◽  
Alcoholic Fatty Liver ◽  
Physiological Processes ◽  
The Relationship ◽  
Alcoholic Fatty Liver Disease

The aim: To analyze the relationship between non-alcoholic fatty liver disease and changes in the gut microbiota. Materials and methods: The publications of domestic and foreign editions in the databases of the United European Gastroenterology (UEG) Journal, PubMed, MEDLINE, Web of Science were processed and analyzed. Conclusions: In recent years, non-alcoholic fatty liver disease was placed among the important diseases in gastroenterology. During this time, more and more data appear on the link between changes in the human intestinal microbiome and the development of metabolic diseases, including NAFLD. Contemporary research has indeed found evidence of such a relationship. Thus, some strains of microorganisms have been identified in more detail, which directly or indirectly affect the development or course of the above-mentioned disease. For a better understanding of the strategies for the treatment of pathologies, it is necessary to delve into the study of etiological factors, therefore, NAFLC cannot be considered a pathology that has been sufficiently studied. Indeed, recent data indicate that the development and severity of the course of the disease are not always associated with the physiological processes already known to us.

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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