Ferroptosis and metabolic dysfunction‐associated fatty liver disease: Is there a link?

Feng, Guohua; Byrne, Christopher D.; Targher, Giovanni; Wang, Fudi; Zheng, Ming‐Hua

doi:10.1111/liv.15163

Cited by 41 publications

(35 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…32 In addition, hepatic iron overload was found to induce oxidative stress and lipid peroxidation by producing reactive oxygen species, consequently triggering ferroptosis. 33 Tsurusaki et al confirmed that hepatic ferroptosis triggers the initiation of inflammation in mice with steatohepatitis. 8 The dysfunction of iron metabolism and involvement of lipid peroxidation in the association between ferroptosis and MAFLD, and the role of iron-chelating agents in the alleviation of histopathological lesions and reduction of hepatic inflammation in mice, were highlighted in further experimental evidence.…”

Section: Discussionmentioning

confidence: 97%

“…Hepatic iron quantified using MRI‐based R2* was reported to be associated with liver fibrosis, hepatic inflammation and ballooning, 6 which may be partly explained by the disruption of the balance between M1/M2 macrophage polarization and the activation of M1 macrophages 32 . In addition, hepatic iron overload was found to induce oxidative stress and lipid peroxidation by producing reactive oxygen species, consequently triggering ferroptosis 33 . Tsurusaki et al confirmed that hepatic ferroptosis triggers the initiation of inflammation in mice with steatohepatitis 8 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Causal relationships between metabolic‐associated fatty liver disease and iron status: Two‐sample Mendelian randomization

Liao

Zeng

et al. 2022

Liver International

View full text Add to dashboard Cite

Background & Aims Dysregulated iron homeostasis plays an important role in the hepatic manifestation of metabolic‐associated fatty liver disease (MAFLD). We investigated the causal effects of five iron metabolism markers, regular iron supplementation and MAFLD risk. Methods Genetic summary statistics were obtained from open genome‐wide association study databases. Two‐sample bidirectional Mendelian randomization analysis was performed to estimate the causal effect between iron status and MAFLD, including Mendelian randomization inverse‐variance weighted, weighted median methods and Mendelian randomization‐Egger regression. The Mendelian randomization‐PRESSO outlier test, Cochran's Q test and Mendelian randomization‐Egger regression were used to assess outliers, heterogeneity and pleiotropy respectively. Results Mendelian randomization inverse‐variance weighted results showed that the genetically predicted per standard deviation increase in liver iron (Data set 2: odds ratio 1.193, 95% confidence interval [CI] 1.074–1.326, p = .001) was associated with an increased MAFLD risk, consistent with the weighted median estimates and Mendelian randomization–Egger regression, although Data set 1 was not significant. Mendelian randomization inverse‐variance weighted analysis showed that genetically predicted MAFLD was significantly associated with increased serum ferritin levels in both datasets (Dataset 1: β = .038, 95% CI = .014 to .062, p = .002; Dataset 2: β = .081, 95% CI = .025 to .136, p = .004), and a similar result was observed with the weighted median methods for Dataset 2 instead of Mendelian randomization‐Egger regression. Conclusions This study uncovered genetically predicted causal associations between iron metabolism status and MAFLD. These findings underscore the need for improved guidelines for managing MAFLD risk by emphasizing hepatic iron levels as a risk factor and ferritin levels as a prognostic factor.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Causal relationships between metabolic‐associated fatty liver disease and iron status: Two‐sample Mendelian randomization

Liao

Zeng

et al. 2022

Liver International

View full text Add to dashboard Cite

show abstract

“…As a newly discovered form of iron-dependent programmed cell death, ferroptosis is involved in the development and progression of NAFLD. 50 A typical feature of NAFLD is the development of oxidative stress and redox imbalance. 51 In recent years, an increasing number of studies reported that coenzyme A is closely related to NAFLD from different perspectives.…”

Section: Discussionmentioning

confidence: 99%

Novel urinary protein panels for the non‐invasive diagnosis of non‐alcoholic fatty liver disease and fibrosis stages

Feng

Zhang

et al. 2023

Liver International

Self Cite

View full text Add to dashboard Cite

Background & Aims: There is an unmet clinical need for non-invasive tests to diagnose non-alcoholic fatty liver disease (NAFLD) and individual fibrosis stages. We aimed to test whether urine protein panels could be used to identify NAFLD, NAFLD with fibrosis (stage F ≥ 1) and NAFLD with significant fibrosis (stage F ≥ 2). Methods: We collected urine samples from 100 patients with biopsy-confirmed NAFLD and 40 healthy volunteers, and proteomics and bioinformatics analyses were performed in this derivation cohort. Diagnostic models were developed for detecting NAFLD (UP NAFLD model), NAFLD with fibrosis (UP fibrosis model), or NAFLD with significant fibrosis (UP significant fibrosis model). Subsequently, the derivation cohort was divided into training and testing sets to evaluate the efficacy of these diagnostic | 1235 FENG et al.

show abstract

“…Liver fibrosis refers to an intricate pathological process in the liver characterized by excessive accumulation of extracellular matrix ( 121 ). It has an intimate association with chronic liver damage and acts as a significant intermediate pathogenetic link of multiple chronic liver disorders, such as NAFLD ( 122 ). If not treated timely, liver fibrosis putatively leads to more detrimental events, including cirrhosis, liver failure, HCC, and even death.…”

Section: The Role Of Ferroptosis In Nafldmentioning

confidence: 99%

Ferroptosis in non-alcoholic liver disease: Molecular mechanisms and therapeutic implications

et al. 2023

View full text Add to dashboard Cite

Ferroptosis refers to a novel modality of regulated cell death characterized by excessive iron accumulation and overwhelming lipid peroxidation, which takes an important part in multiple pathological processes associated with cell death. Considering the crucial roles of the liver in iron and lipid metabolism and its predisposition to oxidative insults, more and more studies have been conducted to explore the relationship between ferroptosis and various liver disorders, including non-alcoholic fatty liver disease (NAFLD). With increased morbidity and high mortality rates, NAFLD has currently emerged as a global public health issue. However, the etiology of NAFLD is not fully understood. In recent years, an accumulating body of evidence have suggested that ferroptosis plays a pivotal role in the pathogenesis of NAFLD, but the precise mechanisms underlying how ferroptosis affects NAFLD still remain obscure. Here, we summarize the molecular mechanisms of ferroptosis and its complicated regulation systems, delineate the different effects that ferroptosis exerts in different stages of NAFLD, and discuss some potential effective therapies targeting ferroptosis for NAFLD treatment, which putatively points out a novel direction for NAFLD treatment.

show abstract

Ferroptosis and metabolic dysfunction‐associated fatty liver disease: Is there a link?

Cited by 41 publications

References 66 publications

Causal relationships between metabolic‐associated fatty liver disease and iron status: Two‐sample Mendelian randomization

Causal relationships between metabolic‐associated fatty liver disease and iron status: Two‐sample Mendelian randomization

Novel urinary protein panels for the non‐invasive diagnosis of non‐alcoholic fatty liver disease and fibrosis stages

Ferroptosis in non-alcoholic liver disease: Molecular mechanisms and therapeutic implications

Contact Info

Product

Resources

About