Computational Modelling of Liver Metabolism and its Applications in Research and the Clinics

Tomaš, Tanja Cvitanović; Moškon, Miha; Mraz, Miha; Rozman, Damjana

doi:10.17344/acsi.2018.4461

Cited by 9 publications

(5 citation statements)

References 86 publications

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“…The authors conclude that GH regulated gene expression is a significant determinant of sexual dimorphic gene expression in the rat liver [ 44 ]. Variation in GH also plays an important role in a recent large scale model of male-female liver dimorphism by the Rozman group (described in the Discussion) [ 45 – 47 ].…”

Section: Resultsmentioning

confidence: 99%

“…Recently, a large scale semi-quantitative model of sex differences in liver metabolism has been published [ 45 – 47 ] based on an earlier model of male liver metabolism [ 65 ]. The authors show that this model, which includes both sex hormone and growth hormone effects, allows a detailed insight into sex-dependent liver pathologies and they use the model to identify the most important sex-dependent pathways involved in non-alcoholic fatty liver disease.…”

Section: Discussionmentioning

confidence: 99%

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Sex differences in hepatic one-carbon metabolism

et al. 2018

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BackgroundThere are large differences between men and women of child-bearing age in the expression level of 5 key enzymes in one-carbon metabolism almost certainly caused by the sex hormones. These male-female differences in one-carbon metabolism are greatly accentuated during pregnancy. Thus, understanding the origin and consequences of sex differences in one-carbon metabolism is important for precision medicine.ResultsWe have created a mathematical model of hepatic one-carbon metabolism based on the underlying physiology and biochemistry. We use the model to investigate the consequences of sex differences in gene expression. We give a mechanistic understanding of observed concentration differences in one-carbon metabolism and explain why women have lower S-andenosylmethionine, lower homocysteine, and higher choline and betaine. We give a new explanation of the well known phenomenon that folate supplementation lowers homocysteine and we show how to use the model to investigate the effects of vitamin deficiencies, gene polymorphisms, and nutrient input changes.ConclusionsOur model of hepatic one-carbon metabolism is a useful platform for investigating the mechanistic reasons that underlie known associations between metabolites. In particular, we explain how gene expression differences lead to metabolic differences between males and females.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-018-0621-7) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sex differences in hepatic one-carbon metabolism

et al. 2018

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“…Several studies have showed that age is a factor associated with the development and severity of liver fibrosis in NAFLD and T2D patients; however, other studies have indicated that the increased probability of liver fibrosis among T2D patients is independent of age [ 25 , 28 , 29 , 30 , 31 , 32 ]. Liver is an organ with age-related changes, and the complications from chronic liver disease increase with age [ 31 , 33 ]. Aging induces metabolic disturbances and promotes lipid accumulation in the liver [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

The Determinants of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus

Fang

Hung

et al. 2022

Biomedicines

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Liver fibrosis is a key pathophysiology process in chronic liver disease. It is still unclear whether the impact of liver fibrosis is not fully realized in type 2 diabetes mellitus (T2D) patients with nonalcoholic fatty liver disease (NAFLD), and the factors affecting nonalcoholic steatohepatitis (NASH) or liver stiffness also remain unclear. The aim of this study was to evaluate the determinants of liver fibrosis and in T2D patients with NAFLD. Liver fibrosis and steatosis were measured using transient elastography (FibroScan). Of 226 T2D patients with NAFLD, 50 with liver fibrosis had higher body mass index, serum uric acid, triglyceride and glycated hemoglobin levels and lower high density lipoprotein levels than 176 without liver fibrosis. Multivariate analysis revealed that aging, obesity, sulfonylurea usage and high levels of AST increased the risk of liver fibrosis in T2D patients with NAFLD. Our findings provide useful information to clinical physicians for earlier detection of liver fibrosis in T2D patients with NAFLD and to prevent liver fibrosis through controlling these risk factors.

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“…Computational models and in silico approaches have acquired great importance along with the evolution of computers and the rising relevance of data science, which allows researchers to investigate large databases in a high-throughput, fast manner. In silico strategies have been developed to study food-drug interactions, liver metabolism modeling, and fibrotic process simulation that recapitulate collagen deposition and inflammatory processes in central venous regions [102][103][104]. However, Drug-Induced Liver Injury (DILI) research stands out as one of the most benefitted areas when it comes to computational models.…”

Section: Computational Modelsmentioning

confidence: 99%

The 3Rs in Experimental Liver Disease

Martinez-Lopez,

Angel-Gomis,

Sanchez-Ardid

et al. 2023

Animals

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Patients with cirrhosis present multiple physiological and immunological alterations that play a very important role in the development of clinically relevant secondary complications to the disease. Experimentation in animal models is essential to understand the pathogenesis of human diseases and, considering the high prevalence of liver disease worldwide, to understand the pathophysiology of disease progression and the molecular pathways involved, due to the complexity of the liver as an organ and its relationship with the rest of the organism. However, today there is a growing awareness about the sensitivity and suffering of animals, causing opposition to animal research among a minority in society and some scientists, but also about the attention to the welfare of laboratory animals since this has been built into regulations in most nations that conduct animal research. In 1959, Russell and Burch published the book “The Principles of Humane Experimental Technique”, proposing that in those experiments where animals were necessary, everything possible should be done to try to replace them with non-sentient alternatives, to reduce to a minimum their number, and to refine experiments that are essential so that they caused the least amount of pain and distress. In this review, a comprehensive summary of the most widely used techniques to replace, reduce, and refine in experimental liver research is offered, to assess the advantages and weaknesses of available experimental liver disease models for researchers who are planning to perform animal studies in the near future.

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Computational Modelling of Liver Metabolism and its Applications in Research and the Clinics

Cited by 9 publications

References 86 publications

Sex differences in hepatic one-carbon metabolism

Sex differences in hepatic one-carbon metabolism

The Determinants of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus

The 3Rs in Experimental Liver Disease

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