Protective role of magnesium isoglycyrrhizinate in non-alcoholic fatty liver disease and the associated molecular mechanisms

AbstractNon-alcoholic fatty liver disease (NAFLD) has been defined as a spectrum of histological abnormalities and is characterized by significant and excessive accumulation of triglycerides in the hepatocytes in patients without alcohol consumption or other diseases. Current studies are targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. Many therapeutic targets have been found and used in clinical studies. Peroxisome proliferator-activated receptors (PPARs) are among the potential targets and have been demonstrated to exert a pivotal role in modulation of NAFLD. Many drugs developed so far are targeted at PPARs. Thus, the aim of this paper is to summarize the roles of PPARs in the treatment of NAFLD.

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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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