Metabolic Disorders and Cancer: Hepatocyte Store-Operated Ca2+ Channels in Nonalcoholic Fatty Liver Disease

2017 ◽  
pp. 595-621 ◽  
Author(s):  
Eunüs S. Ali ◽  
Grigori Y. Rychkov ◽  
Greg J. Barritt
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Nonalcoholic Fatty Liver ◽  
Ca2 Channels

Effects of nonalcoholic fatty liver disease on the development of metabolic disorders

2007 ◽  
Vol 22 (7) ◽  
pp. 1086-1091 ◽  
Author(s):  
Jian-Gao Fan ◽  
Fen Li ◽  
Xiao-Bo Cai ◽  
Yong-De Peng ◽  
Qing-Hong Ao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Nonalcoholic Fatty Liver

scholarly journals Target Deconvolution of Fenofibrate in Nonalcoholic Fatty Liver Disease Using Bioinformatics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Ali Mahmoudi ◽  
Alexandra E. Butler ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Gene Ontology ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathway ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Biological Pathways ◽  
Venn Diagram ◽  
Nonalcoholic Fatty Liver

Background. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of liver damage, affecting ~25% of the global population. NAFLD comprises a spectrum of liver pathologies, from hepatic steatosis to nonalcoholic steatohepatitis (NASH), and may progress to liver fibrosis and cirrhosis. The presence of NAFLD correlates with metabolic disorders such as hyperlipidemia, obesity, blood hypertension, cardiovascular, and insulin resistance. Fenofibrate is an agonist drug for peroxisome proliferator-activated receptor alpha (PPARα), used principally for treatment of hyperlipidemia. However, fenofibrate has recently been investigated in clinical trials for treatment of other metabolic disorders such as diabetes, cardiovascular disease, and NAFLD. The evidence to date indicates that fenofibrate could improve NAFLD. While PPARα is considered to be the main target of fenofibrate, fenofibrate may exert its effect through impact on other genes and pathways thereby alleviating, and possibly reversing, NAFLD. In this study, using bioinformatics tools and gene-drug, gene-diseases databases, we sought to explore possible targets, interactions, and pathways involved in fenofibrate and NAFLD. Methods. We first determined significant protein interactions with fenofibrate in the STITCH database with high confidence (0.7). Next, we investigated the identified proteins on curated targets in two databases, including the DisGeNET and DISEASES databases, to determine their association with NAFLD. We finally constructed a Venn diagram for these two collections (curated genes-NAFLD and fenofibrate-STITCH) to uncover possible primary targets of fenofibrate. Then, Gene Ontology (GO) and KEGG were analyzed to detect the significantly involved targets in molecular function, biological process, cellular component, and biological pathways. A P value < 0.01 was considered the cut-off criterion. We also estimated the specificity of targets with NAFLD by investigating them in disease-gene associations (STRING) and EnrichR (DisGeNET). Finally, we verified our findings in the scientific literature. Results. We constructed two collections, one with 80 protein-drug interactions and the other with 95 genes associated with NAFLD. Using the Venn diagram, we identified 11 significant targets including LEP, SIRT1, ADIPOQ, PPARA, SREBF1, LDLR, GSTP1, VLDLR, SCARB1, MMP1, and APOC3 and then evaluated their biological pathways. Based on Gene Ontology, most of the targets are involved in lipid metabolism, and KEGG enrichment pathways showed the PPAR signaling pathway, AMPK signaling pathway, and NAFLD as the most significant pathways. The interrogation of those targets on authentic disease databases showed they were more specific to both steatosis and steatohepatitis liver injury than to any other diseases in these databases. Finally, we identified three significant genes, APOC3, PPARA, and SREBF1, that showed robust drug interaction with fenofibrate. Conclusion. Fenofibrate may exert its effect directly or indirectly, via modulation of several key targets and pathways, in the treatment of NAFLD.

scholarly journals Nonalcoholic fatty liver disease and the gut microbiome: Are bacteria responsible for fatty liver?

2019 ◽  
Vol 244 (6) ◽  
pp. 408-418 ◽  
Author(s):  
Tien S Dong ◽  
Jonathan P Jacobs
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Microbial Composition ◽  
Future Directions ◽  
Nonalcoholic Fatty Liver

Over the last several years, a growing body of literature has linked the gut microbiome to human health and diseases such as obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). This paper will review the current literature investigating the influence of diets associated with metabolic disorders on the microbiome and how those changes promote susceptibility to metabolic disorders. It will then focus in-depth on the role of the gut microbiome in NAFLD. The review will highlight associations of microbial composition and function with progression of NAFLD in patients and discuss potential mechanisms that link the gut microbiome to NAFLD. Finally, it will address limitations of existing studies along with future directions for microbiome research in NAFLD, including potential microbe-related treatments. Impact statement This invited minireview for the upcoming thematic issue on the microbiome addresses the role of the microbiome in nonalcoholic fatty liver disease (NAFLD). The incidence of NAFLD has increased greatly in recent years in parallel with the rise in obesity and is now believed to have a population prevalence of 20–40%. It is anticipated to soon become the primary cause of liver-related morbidity and mortality, and unfortunately, there are few treatment options. Therefore, there is a critical need for improved understanding of NAFLD pathophysiology to provide new avenues for therapeutic intervention. In this paper, we have reviewed evidence from human and animal model studies that have associated microbiome composition and microbial metabolites with development and progression of NAFLD. We have also discussed proposed mechanisms by which the microbiome could contribute to NAFLD pathogenesis and addressed future directions for this field.

Does physical inactivity cause nonalcoholic fatty liver disease?

2011 ◽  
Vol 111 (6) ◽  
pp. 1828-1835 ◽  
Author(s):  
R. Scott Rector ◽  
John P. Thyfault
Keyword(s):  
Physical Activity ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Daily Living ◽  
Fatty Liver Disease ◽  
Physical Inactivity ◽  
Metabolic Disorders ◽  
Nonalcoholic Fatty Liver ◽  
Daily Living Activity

While physical activity represents a key element in the prevention and management of many chronic diseases, we and others believe that physical inactivity is a primary cause of obesity and associated metabolic disorders. Unfortunately, accumulating evidence suggests that we have engineered physical activity out of our normal daily living activity. One such consequence of our sedentary and excessive lifestyle is nonalcoholic fatty liver disease (NAFLD), which is now considered the most common cause of chronic liver disease in Westernized societies. In this review, we will present evidence that physical inactivity, low aerobic fitness, and overnutrition, either separately or in combination, are an underlying cause of NAFLD.

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