The Role of Resolvins, Protectins and Marensins in Non-Alcoholic Fatty Liver Disease (NAFLD)

Increased triacylglycerols’ (TAG) synthesis, insulin resistance, and prolonged liver lipid storage might lead to the development of non-alcoholic fatty liver disease (NAFLD). Global prevalence of NAFLD has been estimated to be around 25%, with gradual elevation of this ratio along with the increased content of adipose tissue in a body. The initial stages of NAFLD may be reversible, but the exposition to pathological factors should be limited. As dietary factors greatly influence various disease development, scientists try to find dietary components, helping to alleviate the steatosis. These components include n-3 polyunsaturated (PUFA) fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA). This review focused on the role of resolvins, protectins and merensins in NAFLD.

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The role of the gut microbiome and diet in the pathogenesis of non-alcoholic fatty liver disease

Clinical and Molecular Hepatology ◽

10.3350/cmh.2020.0129 ◽

2021 ◽

Vol 27 (1) ◽

pp. 22-43

Author(s):

Erica Jennison ◽

Christopher D. Byrne

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Gut Microbiome ◽

Fatty Liver Disease ◽

Dietary Factors ◽

Current Evidence ◽

Alcoholic Fatty Liver ◽

Close Relationship ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with a prevalence that is increasing in parallel with the global rise in obesity and type 2 diabetes mellitus. The pathogenesis of NAFLD is complex and multifactorial, involving environmental, genetic and metabolic factors. The role of the diet and the gut microbiome is gaining interest as a significant factor in NAFLD pathogenesis. Dietary factors induce alterations in the composition of the gut microbiome (dysbiosis), commonly reflected by a reduction of the beneficial species and an increase in pathogenic microbiota. Due to the close relationship between the gut and liver, altering the gut microbiome can affect liver functions; promoting hepatic steatosis and inflammation. This review summarises the current evidence supporting an association between NAFLD and the gut microbiome and dietary factors. The review also explores potential underlying mechanisms underpinning these associations and whether manipulation of the gut microbiome is a potential therapeutic strategy to prevent or treat NAFLD.

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The Role of PCSK9 in the Pathogenesis of Non-alcoholic Fatty Liver Disease and the Effect of PCSK9 Inhibitors

Current Pharmaceutical Design ◽

10.2174/1381612824666181010123127 ◽

2019 ◽

Vol 24 (31) ◽

pp. 3654-3657 ◽

Cited By ~ 11

Author(s):

Eleni Theocharidou ◽

Marianna Papademetriou ◽

Andromachi Reklou ◽

Alexandros Sachinidis ◽

Chrisoula Boutari ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Liver Lipid ◽

Density Lipoprotein ◽

Statin Treatment ◽

Pcsk9 Inhibitors ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Background: Statin treatment exhibits a beneficial effect on non-alcoholic fatty liver disease (NAFLD) and on cardiovascular disease (CVD) in patients with NAFLD. Objective: The aim of this review is to summarize the role of proprotein convertase subtilisin kexin type- 9(PCSK9) in the pathogenesis of NAFLD and discuss the effects of the new hypolipidaemic drugs PCSK9 inhibitors on NAFLD. Results: Data indicates that high intrahepatic or circulating PCSK9 levels increase muscle and liver lipid storage, adipose energy storage and hepatic fatty acids, as well as triglycerides storage and secretion, thus contributing to the pathogenesis of NAFLD. The findings of animal and human studies, aiming to reduce PCSK9 with inhibitors (human IGG antibodies, antisense particles against PCSK9 mRNA, and small anti PCSK9 antibodies) point towards liver protection from NAFLD through inhibition of PCSK9 expression in the induction of degradation of hepatic HNF1a protein, insulin resistance (IR), and other mechanisms. Conclusions: The use of PCSK9 inhibitors ameliorates NAFLD, aside from beneficial effects on CVD and independently of low density lipoprotein cholesterol level reduction.

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The Role of the Transsulfuration Pathway in Non-Alcoholic Fatty Liver Disease

Journal of Clinical Medicine ◽

10.3390/jcm10051081 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1081

Author(s):

Mikkel Parsberg Werge ◽

Adrian McCann ◽

Elisabeth Douglas Galsgaard ◽

Dorte Holst ◽

Anne Bugge ◽

...

Keyword(s):

Liver Disease ◽

Animal Models ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Precise Control ◽

Transsulfuration Pathway ◽

Global Population ◽

Alcoholic Fatty Liver Disease

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing and approximately 25% of the global population may have NAFLD. NAFLD is associated with obesity and metabolic syndrome, but its pathophysiology is complex and only partly understood. The transsulfuration pathway (TSP) is a metabolic pathway regulating homocysteine and cysteine metabolism and is vital in controlling sulfur balance in the organism. Precise control of this pathway is critical for maintenance of optimal cellular function. The TSP is closely linked to other pathways such as the folate and methionine cycles, hydrogen sulfide (H2S) and glutathione (GSH) production. Impaired activity of the TSP will cause an increase in homocysteine and a decrease in cysteine levels. Homocysteine will also be increased due to impairment of the folate and methionine cycles. The key enzymes of the TSP, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), are highly expressed in the liver and deficient CBS and CSE expression causes hepatic steatosis, inflammation, and fibrosis in animal models. A causative link between the TSP and NAFLD has not been established. However, dysfunctions in the TSP and related pathways, in terms of enzyme expression and the plasma levels of the metabolites (e.g., homocysteine, cystathionine, and cysteine), have been reported in NAFLD and liver cirrhosis in both animal models and humans. Further investigation of the TSP in relation to NAFLD may reveal mechanisms involved in the development and progression of NAFLD.

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The Role of Oxidative Stress in NAFLD–NASH–HCC Transition—Focus on NADPH Oxidases

Biomedicines ◽

10.3390/biomedicines9060687 ◽

2021 ◽

Vol 9 (6) ◽

pp. 687

Author(s):

Daniela Gabbia ◽

Luana Cannella ◽

Sara De De Martin

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Current Knowledge ◽

Mechanisms Of Action ◽

Nadph Oxidases ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.

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Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients

World Journal of Gastroenterology ◽

10.3748/wjg.v23.i10.1881 ◽

2017 ◽

Vol 23 (10) ◽

pp. 1881 ◽

Cited By ~ 19

Author(s):

Shira Zelber-Sagi ◽

Shiran Bord ◽

Gali Dror-Lavi ◽

Matthew Lee Smith ◽

Samuel D Towne Jr ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Self Efficacy ◽

Fatty Liver Disease ◽

Lifestyle Modification ◽

Illness Perception ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

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A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies

Cells ◽

10.3390/cells10071822 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1822

Author(s):

Christian von Loeffelholz ◽

Sina M. Coldewey ◽

Andreas L. Birkenfeld

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Mammalian Cells ◽

De Novo ◽

Adenosine Monophosphate ◽

De Novo Lipogenesis ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

5′AMP-activated protein kinase (AMPK) is known as metabolic sensor in mammalian cells that becomes activated by an increasing adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio. The heterotrimeric AMPK protein comprises three subunits, each of which has multiple phosphorylation sites, playing an important role in the regulation of essential molecular pathways. By phosphorylation of downstream proteins and modulation of gene transcription AMPK functions as a master switch of energy homeostasis in tissues with high metabolic turnover, such as the liver, skeletal muscle, and adipose tissue. Regulation of AMPK under conditions of chronic caloric oversupply emerged as substantial research target to get deeper insight into the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Evidence supporting the role of AMPK in NAFLD is mainly derived from preclinical cell culture and animal studies. Dysbalanced de novo lipogenesis has been identified as one of the key processes in NAFLD pathogenesis. Thus, the scope of this review is to provide an integrative overview of evidence, in particular from clinical studies and human samples, on the role of AMPK in the regulation of primarily de novo lipogenesis in human NAFLD.

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