scholarly journals Emerging Roles of Calcium Signaling in the Development of Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 23 (1) ◽  
pp. 256
Author(s):  
Chien-Chih Chen ◽  
Li-Wen Hsu ◽  
Kuang-Den Chen ◽  
King-Wah Chiu ◽  
Chao-Long Chen ◽  
...  

The liver plays a central role in energy metabolism. Dysregulated hepatic lipid metabolism is a major cause of non-alcoholic fatty liver disease (NAFLD), a chronic liver disorder closely linked to obesity and insulin resistance. NAFLD is rapidly emerging as a global health problem with currently no approved therapy. While early stages of NAFLD are often considered benign, the disease can progress to an advanced stage that involves chronic inflammation, with increased risk for developing end-stage disease including fibrosis and liver cancer. Hence, there is an urgent need to identify potential pharmacological targets. Ca2+ is an essential signaling molecule involved in a myriad of cellular processes. Intracellular Ca2+ is intricately compartmentalized, and the Ca2+ flow is tightly controlled by a network of Ca2+ transport and buffering proteins. Impaired Ca2+ signaling is strongly associated with endoplasmic reticulum stress, mitochondrial dysfunction and autophagic defects, all of which are etiological factors of NAFLD. In this review, we describe the recent advances that underscore the critical role of dysregulated Ca2+ homeostasis in lipid metabolic abnormalities and discuss the feasibility of targeting Ca2+ signaling as a potential therapeutic approach.

2020 ◽  
Vol 18 (2) ◽  
pp. 22-27
Author(s):  
David Mantle ◽  
Iain P Hargreaves

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in the UK, for which little effective conventional treatment is available. Mitochondrial dysfunction, oxidative stress and inflammation have been implicated in the pathogenesis of NAFLD. This article focuses on the role of the vitamin-like substance coenzyme Q10 (CoQ10) in NAFLD, since CoQ10 plays a key role in mitochondrial function, as well as having antioxidant and anti-inflammatory action. CoQ10 levels are depleted in NAFLD, and studies in animal models and human subjects have indicated that supplementation with CoQ10 can significantly reduce oxidative stress and the inflammation characteristic of NAFLD. In addition, NAFLD patients are at increased risk of developing heart failure, and supplementary CoQ10 may help to reduce this risk. Supplementary CoQ10 is generally well tolerated, with no significant adverse effects reported in long-term use.


2020 ◽  
Vol 2 (4) ◽  
pp. 200-204
Author(s):  
David Mantle ◽  
Iain P Hargreaves

Non-alcoholic fatty liver disease is the most common liver disorder in the UK, for which little effective conventional treatment is available. Mitochondrial dysfunction, oxidative stress and inflammation have been implicated in the pathogenesis of non-alcoholic fatty liver disease. This article focuses on the role of the vitamin-like substance coenzyme Q10 in non-alcoholic fatty liver disease, since coenzyme Q10 plays a key role in mitochondrial function, as well as having antioxidant and anti-inflammatory action. Coenzyme Q10 levels are depleted in non-alcoholic fatty liver disease, and studies in animal models and human subjects have indicated that supplementation with coenzyme Q10 can significantly reduce oxidative stress and the inflammation characteristic of non-alcoholic fatty liver disease. In addition, Non-alcoholic fatty liver disease patients are at increased risk of developing heart failure, and supplementary coenzyme Q10 may help to reduce this risk. Supplementary coenzyme Q10 is generally well tolerated, with no significant adverse effects reported in long-term use.


2010 ◽  
Vol 69 (2) ◽  
pp. 211-220 ◽  
Author(s):  
J. Bernadette Moore

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.


Author(s):  
Claudio Tana ◽  
Stefano Ballestri ◽  
Fabrizio Ricci ◽  
Angelo Di Vincenzo ◽  
Andrea Ticinesi ◽  
...  

New evidence suggests that non-alcoholic fatty liver disease (NAFLD) has a strong multifaceted relationship with diabetes and metabolic syndrome, and is associated with increased risk of cardiovascular events, regardless of traditional risk factors, such as hypertension, diabetes, dyslipidemia, and obesity. Given the pandemic-level rise of NAFLD—in parallel with the increasing prevalence of obesity and other components of the metabolic syndrome—and its association with poor cardiovascular outcomes, the question of how to manage NAFLD properly, in order to reduce the burden of associated incident cardiovascular events, is both timely and highly relevant. This review aims to summarize the current knowledge of the association between NAFLD and cardiovascular disease, and also to discuss possible clinical strategies for cardiovascular risk assessment, as well as the spectrum of available therapeutic strategies for the prevention and treatment of NAFLD and its downstream events.


2019 ◽  
Vol 16 (1) ◽  
pp. 39-45
Author(s):  
Cemal Kemaloglu ◽  
Melek Didem Kemaloglu

Objective: The aim of this study is to identify the relationship between carotid intima-media thickness (c-imt) and non-alcoholic fatty liver disease (NAFLD), and to determine whether NAFLD is an independent predictor for the progression of atherosclerosis.  Method: This is a prospective randomized controlled study. 103 NAFLD patients who have hepatosteatosis with grade II and above were enrolled in this study. Patients were divided into NAFLD with metabolic syndrome (MS) and NAFLD without MS groups and compared with 50 healthy people. Basal demographic characteristics and C-imt of all patients and control group were measured.  Results: C-imt and carotid cross sectional area rates in the NAFLD groups were significantly higher than those in the control group. The mean and max. c-imt levels were significantly higher in the NAFLD group with metabolic syndrome (p<0,001). Homeostatic Model of Assessment-Insulin Resistance (HOMA-IR) levels were increased in the group with metabolic syndrome than those in the group without metabolic syndrome, with statistical significance (p<0.001). There was no difference in c-imt levels between HOMA-IR positive and negative groups (p=0.254) in patients with NAFLD and without metabolic syndrome. There was only a mild positive corelation between c-imt levels and high sensitive C-Reactive protein (hs-CRP) levels in metabolic syndrome positive group (p=0.026 r=0.30).  Conclusion: NAFLD was a significant predictor to determine the increased risk of carotid atherosclerosis. 


2019 ◽  
Vol 20 (9) ◽  
pp. 2215 ◽  
Author(s):  
Hamza El Hadi ◽  
Angelo Di Vincenzo ◽  
Roberto Vettor ◽  
Marco Rossato

With the progressive epidemics of obesity, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in adults and children. The increasing prevalence and incidence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher non-liver-related morbidity and mortality than the general population. Recent clinical evidence suggests that NAFLD is directly associated with an increased risk of cardio-metabolic disorders. This mini review describes briefly the current understanding of the pathogenesis of NAFLD, summarizing the link between NAFLD and cardio-metabolic complications, focusing mainly upon ischemic stroke, type 2 diabetes mellitus (DM), hypertension, chronic kidney disease (CKD) and cardiac arrhythmias. In addition, it describes briefly the current understanding of the pathogenesis of NAFLD.


Author(s):  
R. Mark Beattie ◽  
Anil Dhawan ◽  
John W.L. Puntis

Demographics 406Pathophysiology 406Differential diagnoses 407Presenting features 407Investigation 408Management 409Fatty liver disease is now increasingly recognized in children, particularly in the setting of obesity.The term non-alcoholic steatohepatitis (NASH) was first coined in 1980 by Ludwig to describe a pattern of liver injury in adults in which the liver histology was consistent with alcoholic hepatitis, but in whom significant alcohol consumption was denied. NASH can be considered as part of a broader spectrum of non-alcoholic fatty liver disease that extends from simple steatosis through steatohepatitis that is characterized by the potential to progress to fibrosis, cirrhosis and subsequent end stage liver disease....


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