Systems biology for hepatologists

Mato, José M.; Martínez‐Chantar, María Luz; Lu, Shelly C.

doi:10.1002/hep.27023

Cited by 15 publications

(6 citation statements)

References 51 publications

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“…To gain insight into the etiology of NAFLD, we have employed a ‘systems genetics’ strategy to generate a comprehensive view of the genetic architecture of NAFLD in mice ( Civelek and Lusis, 2014 ; Mato et al, 2014 ). We examined natural variations in the development of steatosis in a panel of inbred strains of mice fed a high-fat, high-sucrose (HF/HS) diet for 8 weeks.…”

Section: Introductionmentioning

confidence: 99%

The genetic architecture of NAFLD among inbred strains of mice

Hui

Parks

Org

et al. 2015

eLife

117

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To identify genetic and environmental factors contributing to the pathogenesis of non-alcoholic fatty liver disease, we examined liver steatosis and related clinical and molecular traits in more than 100 unique inbred mouse strains, which were fed a diet rich in fat and carbohydrates. A >30-fold variation in hepatic TG accumulation was observed among the strains. Genome-wide association studies revealed three loci associated with hepatic TG accumulation. Utilizing transcriptomic data from the liver and adipose tissue, we identified several high-confidence candidate genes for hepatic steatosis, including Gde1, a glycerophosphodiester phosphodiesterase not previously implicated in triglyceride metabolism. We confirmed the role of Gde1 by in vivo hepatic over-expression and shRNA knockdown studies. We hypothesize that Gde1 expression increases TG production by contributing to the production of glycerol-3-phosphate. Our multi-level data, including transcript levels, metabolite levels, and gut microbiota composition, provide a framework for understanding genetic and environmental interactions underlying hepatic steatosis.DOI: http://dx.doi.org/10.7554/eLife.05607.001

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Section: Introductionmentioning

confidence: 99%

The genetic architecture of NAFLD among inbred strains of mice

Hui

Parks

Org

et al. 2015

eLife

117

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“…Bulk liver transcriptomics were the first to investigate NAFLD, and are still the most common, but are disproportionately dominated by the parenchymal hepatocytes, which make up 60-70% of the cells in the healthy liver ( Figure 2). Bulk transcriptomics therefore has limited value for the analysis of less abundant cell types [57]. Bulk transcriptomics studies in human NAFLD and steatohepatitis have described changes to genes involved in lipid handling, inflammation, cell migration, extracellular matrix turnover, and regenerative processes [58,59].…”

Section: Transcriptomicsmentioning

confidence: 99%

The Role of Diagnostic Biomarkers, Omics Strategies, and Single-Cell Sequencing for Nonalcoholic Fatty Liver Disease in Severely Obese Patients

Wernberg

Ravnskjær

Lauridsen

et al. 2021

JCM

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Liver disease due to metabolic dysfunction constitute a worldwide growing health issue. Severe obesity is a particularly strong risk factor for non-alcoholic fatty liver disease, which affects up to 93% of these patients. Current diagnostic markers focus on the detection of advanced fibrosis as the major predictor of liver-related morbidity and mortality. The most accurate diagnostic tools use elastography to measure liver stiffness, with diagnostic accuracies similar in normal-weight and severely obese patients. The effectiveness of elastography tools are however hampered by limitations to equipment and measurement quality in patients with very large abdominal circumference and subcutaneous fat. Blood-based biomarkers are therefore attractive, but those available to date have only moderate diagnostic accuracy. Ongoing technological advances in omics technologies such as genomics, transcriptomics, and proteomics hold great promise for discovery of biomarkers and increased pathophysiological understanding of non-alcoholic liver disease and steatohepatitis. Very recent developments have allowed for single-cell sequencing and cell-type resolution of gene expression and function. In the near future, we will therefore likely see a multitude of breakthrough biomarkers, developed from a deepened understanding of the biological function of individual cell types in the healthy and injured liver.

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“…Systems biology is the computational and mathematical modeling of complex biological systems to better understand and predict the phenotypical outcomes. The field includes metabolomics, genomics, proteomics, transcriptomics, and epigenomics, which collectively are called omics [ 14 ].…”

Section: Liver Disease and Micrornasmentioning

confidence: 99%

MicroRNAs in the Evaluation and Potential Treatment of Liver Diseases

Mahgoub

Steer

2016

JCM

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Acute and chronic liver disease continue to result in significant morbidity and mortality of patients, along with increasing burden on their families, society and the health care system. This in part is due to increased incidence of liver disease associated factors such as metabolic syndrome; improved survival of patients with chronic predisposing conditions such as HIV; as well as advances in the field of transplantation and associated care leading to improved survival. The fact that one disease can result in different manifestations and outcomes highlights the need for improved understanding of not just genetic phenomenon predisposing to a condition, but additionally the role of epigenetic and environmental factors leading to the phenotype of the disease. It is not surprising that providers continue to face daily challenges pertaining to diagnostic accuracy, prognostication of disease severity, progression, and response to therapies. A number of these challenges can be addressed by incorporating a personalized approach of management to the current paradigm of care. Recent advances in the fields of molecular biology and genetics have paved the way to more accurate, individualized and precise approach to caring for liver disease. The study of microRNAs and their role in both healthy and diseased livers is one example of such advances. As these small, non-coding RNAs work on fine-tuning of cellular activities and organ function in a dynamic and precise fashion, they provide us a golden opportunity to advance the field of hepatology. The study of microRNAs in liver disease promises tremendous improvement in hepatology and is likely to lay the foundation towards a personalized approach in liver disease.

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Systems biology for hepatologists

Cited by 15 publications

References 51 publications

The genetic architecture of NAFLD among inbred strains of mice

The genetic architecture of NAFLD among inbred strains of mice

The Role of Diagnostic Biomarkers, Omics Strategies, and Single-Cell Sequencing for Nonalcoholic Fatty Liver Disease in Severely Obese Patients

MicroRNAs in the Evaluation and Potential Treatment of Liver Diseases

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