Role of Ferroptosis in Non-Alcoholic Fatty Liver Disease and Its Implications for Therapeutic Strategies

Zhang, Han; Zhang, Enxiang; Hu, Hongbo

doi:10.3390/biomedicines9111660

Cited by 44 publications

(51 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In that context, Nrf2 and GPx4 stand out as major protective mechanisms. 114,136 Overall, the results imply that the regulation of ferroptosis in the context of NAFLD is an intriguing notion that deserves further investigation.…”

Section: Ferroptosis In Nafldmentioning

confidence: 76%

The Gut Microbiome and Ferroptosis in MAFLD

Ji¹,

Wu²,

Wei³

et al. 2022

J Clin Transl Hepatol

View full text Add to dashboard Cite

Metabolic-associated fatty liver disease (MAFLD) is a new disease definition, and is proposed to replace the previous name, nonalcoholic fatty liver disease (NAFLD). Globally, MAFLD/NAFLD is the most common liver disease, with an incidence rate ranging from 6% to 35% in adult populations. The pathogenesis of MAFLD/NAFLD is closely related to insulin resistance (IR), and the genetic susceptibility to acquired metabolic stress-associated liver injury. Similarly, the gut microbiota in MAFLD/NAFLD is being revaluated by scientists, as the gut and liver influence each other via the gut-liver axis. Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation. Emerging evidence suggests that ferroptosis has a key role in the pathological progression of MAFLD/NAFLD, and inhibition of ferroptosis may become a novel therapeutic strategy for the treatment of NAFLD. This review focuses on the main mechanisms behind the promotion of MAFLD/NAFLD occurrence and development by the intestinal microbiota and ferroptosis. It outlines new strategies to target the intestinal microbiota and ferroptosis to facilitate future MAFLD/NAFLD therapies.

show abstract

Section: Ferroptosis In Nafldmentioning

confidence: 76%

The Gut Microbiome and Ferroptosis in MAFLD

Ji¹,

Wu²,

Wei³

et al. 2022

J Clin Transl Hepatol

View full text Add to dashboard Cite

show abstract

“…In this study, ferroptosis ( Figure 2F ), ROS metabolic process ( Figures 3A,B ), and NAFLD (containing IL-6, BID, PRKAA2) signaling were identified as the activated biological processes or pathways involved in CAVD, and particularly, NAFLD was validated by WebGestalt, DAVID, and Metascape, which was consistent with the previous findings ( 6 , 21 ). Iron overload was observed in patients with NAFLD and the liver damage could be attenuated by iron removal ( 22 , 23 ). Therefore, the pathological process of NAFLD is closely associated with ferroptosis due to iron overload and lipid peroxidation ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

“…Iron overload was observed in patients with NAFLD and the liver damage could be attenuated by iron removal ( 22 , 23 ). Therefore, the pathological process of NAFLD is closely associated with ferroptosis due to iron overload and lipid peroxidation ( 23 ). In addition, it was shown that iron deposits and penetration of senescent erythrocytes into the lea?et fibrosa comprised a central component not only of the initiation but also of the progression of CAVD ( 6 ).…”

Section: Discussionmentioning

confidence: 99%

Potential ferroptosis key genes in calcific aortic valve disease

Xiong

Zhang

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Calcific aortic valve disease (CAVD) is a highly prevalent condition that comprises a disease continuum, ranging from microscopic changes to profound fibro-calcific leaflet remodeling, culminating in aortic stenosis, heart failure, and ultimately premature death. Ferroptosis has been hypothesized to contribute to the pathogenesis of CAVD. We aimed to study the association between ferroptosis genes and CAVD and reveal the potential roles of ferroptosis in CAVD. CAVD-related differentially expressed genes (DEGs) were identified via bioinformatic analysis of Datasets GSE51472 and GSE12644 obtained from Gene Expression Omnibus. A ferroptosis dataset containing 259 genes was obtained from the Ferroptosis Database. We then intersected with CAVD-related DEGs to identify the ferroptosis DEGs. Subsequently, protein–protein interaction networks and functional enrichment analyses were performed for ferroptosis DEGs. Then, we used miRWalk3.0 to predict the target pivotal microRNAs. An in vitro model of CAVD was constructed using human aortic valve interstitial cells. The qRT-PCR and western blotting methods were used to validate the ferroptosis DEGs identified by the microarray data. A total of 21 ferroptosis DEGs in CAVD containing 12 upregulated and nine downregulated genes were identified. The results of the Gene Set Enrichment Analysis (GSEA) and analysis of the KEGG pathway by WebGestalt indicated that the ferroptosis DEGs were enriched in six signaling pathways among which NAFLD (including IL-6, BID, and PRKAA2 genes) and HIF-1 (including IL-6, HIF-1, and HMOX1 genes) signaling pathways were also verified by DAVID and/or Metascape. Finally, the in vitro results showed that the mRNA and protein expression levels of IL-6, HIF-1α, HMOX1, and BID were higher, while the levels of PRKAA2 were lower in the Pi-treated group than those in the control group. However, the addition of ferrostatin-1 (a selective ferroptosis inhibitor) significantly reversed the above changes. Therefore, IL-6, HIF-1α, HMOX1, BID, and PRKAA2 are potential key genes closely associated with ferroptosis in CAVD. Further work is required to explore the underlying ferroptosis-related molecular mechanisms and provide possible therapeutic targets for CAVD.

show abstract

“…The PCD pathways mentioned above may be activated at different stages of NAFLD, and the key effector molecules involved are also the focus of attention when developing therapeutic agents for NAFLD. Therefore, targeting the modulation of the PCD pathway is an effective approach to prevent or treat NAFLD/NAFLD-HCC (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Protective effect of traditional Chinese medicine on non-alcoholic fatty liver disease and liver cancer by targeting ferroptosis

Chen

Ding

et al. 2022

Front. Nutr.

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with high incidence and is closely related to metabolic syndrome. If not controlled, it may eventually become hepatocellular carcinoma (HCC). Ferroptosis, a non-apoptotic form of programmed cell death (PCD), is closely related to NAFLD and HCC, and the mechanisms of action involved are more complex. Some studies have demonstrated that many drugs inhibit ferroptosis and protect liver steatosis or carcinogenesis. The role of Traditional Chinese Medicine (TCM), especially herbs or herbal extracts, has received increasing attention. However, there are relatively few review articles on the regulation of NAFLD by TCM through ferroptosis pathway. Here, we summarize the TCM intervention mechanism and application affecting NAFLD/NAFLD-HCC via regulation of ferroptosis. This article focuses on the relationship between ferroptosis and NAFLD or NAFLD-HCC and the protective effect of TCM on both by targeting ferroptosis. It not only summarizes the mechanism of early prevention and treatment of NAFLD, but also provides reference ideas for the development of TCM for the treatment of metabolic diseases and liver diseases.

show abstract

Role of Ferroptosis in Non-Alcoholic Fatty Liver Disease and Its Implications for Therapeutic Strategies

Cited by 44 publications

References 116 publications

The Gut Microbiome and Ferroptosis in MAFLD

The Gut Microbiome and Ferroptosis in MAFLD

Potential ferroptosis key genes in calcific aortic valve disease

Protective effect of traditional Chinese medicine on non-alcoholic fatty liver disease and liver cancer by targeting ferroptosis

Contact Info

Product

Resources

About