scholarly journals From sugar to liver fat and public health: systems biology driven studies in understanding non-alcoholic fatty liver disease pathogenesis

2019 ◽  
Vol 78 (3) ◽  
pp. 290-304 ◽  
Author(s):  
J. Bernadette Moore
Keyword(s):  
Public Health ◽  
Liver Disease ◽  
Systems Biology ◽  
Fatty Liver ◽  
Chronic Diseases ◽  
Fatty Liver Disease ◽  
Health Concern ◽  
Alcoholic Fatty Liver ◽  
Genome Scale ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now a major public health concern with an estimated prevalence of 25–30% of adults in many countries. Strongly associated with obesity and the metabolic syndrome, the pathogenesis of NAFLD is dependent on complex interactions between genetic and environmental factors that are not completely understood. Weight loss through diet and lifestyle modification underpins clinical management; however, the roles of individual dietary nutrients (e.g. saturated and n-3 fatty acids; fructose, vitamin D, vitamin E) in the pathogenesis or treatment of NAFLD are only partially understood. Systems biology offers valuable interdisciplinary methods that are arguably ideal for application to the studying of chronic diseases such as NAFLD, and the roles of nutrition and diet in their molecular pathogenesis. Although present in silico models are incomplete, computational tools are rapidly evolving and human metabolism can now be simulated at the genome scale. This paper will review NAFLD and its pathogenesis, including the roles of genetics and nutrition in the development and progression of disease. In addition, the paper introduces the concept of systems biology and reviews recent work utilising genome-scale metabolic networks and developing multi-scale models of liver metabolism relevant to NAFLD. A future is envisioned where individual genetic, proteomic and metabolomic information can be integrated computationally with clinical data, yielding mechanistic insight into the pathogenesis of chronic diseases such as NAFLD, and informing personalised nutrition and stratified medicine approaches for improving prognosis.

scholarly journals Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome

2010 ◽  
Vol 69 (2) ◽  
pp. 211-220 ◽  
Author(s):  
J. Bernadette Moore
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Response To Treatment ◽  
Health Concern ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.

scholarly journals Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Tuulia Hyötyläinen ◽  
Livnat Jerby ◽  
Elina M. Petäjä ◽  
Ismo Mattila ◽  
Sirkku Jäntti ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Genome Scale ◽  
Alcoholic Fatty Liver Disease

scholarly journals Hypoxia-Inducible Factors as Key Players in the Pathogenesis of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Lorenz M. W. Holzner ◽  
Andrew J. Murray
Keyword(s):  
Transcription Factors ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Treatment Options ◽  
Redox Homeostasis ◽  
Health Concern ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) are a major public health concern with high and increasing global prevalence, and a significant disease burden owing to its progression to more severe forms of liver disease and the associated risk of cardiovascular disease. Treatment options, however, remain scarce, and a better understanding of the pathological and physiological processes involved could enable the development of new therapeutic strategies. One process implicated in the pathology of NAFLD and NASH is cellular oxygen sensing, coordinated largely by the hypoxia-inducible factor (HIF) family of transcription factors. Activation of HIFs has been demonstrated in patients and mouse models of NAFLD and NASH and studies of activation and inhibition of HIFs using pharmacological and genetic tools point toward important roles for these transcription factors in modulating central aspects of the disease. HIFs appear to act in several cell types in the liver to worsen steatosis, inflammation, and fibrosis, but may nevertheless improve insulin sensitivity. Moreover, in liver and other tissues, HIF activation alters mitochondrial respiratory function and metabolism, having an impact on energetic and redox homeostasis. This article aims to provide an overview of current understanding of the roles of HIFs in NAFLD, highlighting areas where further research is needed.

scholarly journals Non-Alcoholic Fatty Liver Disease in Lean and Non-Obese Individuals: Current and Future Challenges

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1346
Author(s):  
Mohammad Shafi Kuchay ◽  
José Ignacio Martínez-Montoro ◽  
Narendra Singh Choudhary ◽  
José Carlos Fernández-García ◽  
Bruno Ramos-Molina
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Current Treatment ◽  
Normal Weight ◽  
Health Concern ◽  
Excess Body Weight ◽  
Alcoholic Fatty Liver ◽  
Lean Nafld ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD), which approximately affects a quarter of the world’s population, has become a major public health concern. Although usually associated with excess body weight, it may also affect normal-weight individuals, a condition termed as lean/non-obese NAFLD. The prevalence of lean/non-obese NAFLD is around 20% within the NAFLD population, and 5% within the general population. Recent data suggest that individuals with lean NAFLD, despite the absence of obesity, exhibit similar cardiovascular- and cancer-related mortality compared to obese NAFLD individuals and increased all-cause mortality risk. Lean and obese NAFLD individuals share several metabolic abnormalities, but present dissimilarities in genetic predisposition, body composition, gut microbiota, and susceptibility to environmental factors. Current treatment of lean NAFLD is aimed at improving overall fitness and decreasing visceral adiposity, with weight loss strategies being the cornerstone of treatment. Moreover, several drugs including PPAR agonists, SGLT2 inhibitors, or GLP-1 receptor agonists could also be useful in the management of lean NAFLD. Although there has been an increase in research regarding lean NAFLD, there are still more questions than answers. There are several potential drugs for NAFLD therapy, but clinical trials are needed to evaluate their efficacy in lean individuals.

Metabolic disturbances in non-alcoholic fatty liver disease

2009 ◽  
Vol 116 (7) ◽  
pp. 539-564 ◽  
Author(s):  
Christopher D. Byrne ◽  
Rasaq Olufadi ◽  
Kimberley D. Bruce ◽  
Felino R. Cagampang ◽  
Mohamed H. Ahmed
Keyword(s):  
Public Health ◽  
Liver Disease ◽  
Fatty Liver ◽  
Health Problem ◽  
Fatty Liver Disease ◽  
Public Health Problem ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Alcoholic Fatty Liver Disease ◽  
Over Time

NAFLD (non-alcoholic fatty liver disease) refers to a wide spectrum of liver damage, ranging from simple steatosis to NASH (non-alcoholic steatohepatitis), advanced fibrosis and cirrhosis. NAFLD is strongly associated with insulin resistance and is defined by accumulation of liver fat >5% per liver weight in the presence of <10 g of daily alcohol consumption. The exact prevalence of NAFLD is uncertain because of the absence of simple non-invasive diagnostic tests to facilitate an estimate of prevalence. In certain subgroups of patients, such as those with Type 2 diabetes, the prevalence of NAFLD, defined by ultrasound, may be as high as 70%. NASH is an important subgroup within the spectrum of NAFLD that progresses over time with worsening fibrosis and cirrhosis, and is associated with increased risk for cardiovascular disease. It is, therefore, important to understand the pathogenesis of NASH and, in particular, to develop strategies for interventions to treat this condition. Currently, the ‘gold standard’ for the diagnosis of NASH is liver biopsy, and the need to undertake a biopsy has impeded research in subjects in this field. Limited results suggest that the prevalence of NASH could be as high as 11% in the general population, suggesting there is a worsening future public health problem in this field of medicine. With a burgeoning epidemic of diabetes in an aging population, it is likely that the prevalence of NASH will continue to increase over time as both factors are important risk factors for liver fibrosis. The purpose of this review is to: (i) briefly discuss the epidemiology of NAFLD to describe the magnitude of the future potential public health problem; and (ii) to discuss extra- and intra-hepatic mechanisms contributing to the pathogenesis of NAFLD, a better understanding of which may help in the development of novel treatments for this condition.

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