Genomic Exploration of Nonalcoholic Fatty Liver Disease: Insights From Gene Expression and Variation in Morbidly Obese Individuals DOI Creative Commons

Tamadher Abbas Rafaa,

Safa Abbas Khudhair,

Zainab O. Mohammed

et al.

Journal of Obesity, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Nonalcoholic fatty liver disease (NAFLD) is a common condition resulting from metabolic syndrome characterized by fat accumulation in the liver. It often associated with obesity and diabetes, contributing to hepatic steatosis cells. The prevalence of NAFLD increasing globally, 32% adult population affected. Genetic modifiers, such as single nucleotide polymorphisms, can increase susceptibility disease. Gene expression analysis genetic variation help identify disease‐causing pathways reveal biomarkers involved NAFLD. This study employed integrative bioinformatics analysis, including bulk RNA‐seq single‐cell RNA‐seq, explore differentially expressed genes their variants vs. control cirrhosis, highlighting influencing progression. Moreover, this identified AKR1D1, LIPC, UGT2B17, DGAT2, SERPINE1 implicated metabolic, immune, lipid functions while being overexpressed both hepatocyte cells among obese patients validated through Liver Cell Atlas, pivotal role pathogenesis perturbed hepatocytes. Furthermore, novel pathogenic , congenital bile acid synthesis defects, abnormal circulating concentrations, plasminogen activator inhibitor type 1 deficiency conditions, were identified. Conclusively, multiomics highlights AKR1D1 LIPC that are highly hepatocytes possibly carrying mutations may be NAFLD, emphasizing potential targets for therapeutic strategies biomarker development early diagnosis treatment before onset cirrhosis or hepatocellular carcinoma.

Language: Английский

Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway DOI Creative Commons

Tianyu Jiang,

Yao Xiao, Jinfeng Zhou

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 68, P. 102963 - 102963

Published: Nov. 16, 2023

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious that affects 30 % of the global population and poses significant risk to human health. However, date, no safe, effective appropriate treatment modalities are available. In recent years, ferroptosis has emerged as mode cell death been found play key regulatory role in development NAFLD. this study, we arbutin (ARB), natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits onset ameliorates high-fat diet-induced NAFLD vivo vitro. Using reverse docking, identified demethylase fat mass obesity-related protein (FTO) potential target ARB. Subsequent mechanistic studies revealed ARB plays controlling methylation SLC7A11 gene through inhibition FTO. addition, demonstrated could alleviate Our findings identify FTO/SLC7A11 axis therapeutic for Specifically, show alleviates by acting on pathway inhibit ferroptosis.

Language: Английский

Citations

36
The crosstalk between mitochondrial quality control and metal-dependent cell death DOI Creative Commons

Qi-yuan Zhou,

Chao Ren,

Jing‐Yan Li

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 27, 2024

Abstract Mitochondria are the centers of energy and material metabolism, they also serve as storage dispatch hubs metal ions. Damage to mitochondrial structure function can cause abnormal levels distribution ions, leading cell dysfunction even death. For a long time, quality control pathways such dynamics mitophagy have been considered inhibit metal-induced However, with discovery new metal-dependent death including ferroptosis cuproptosis, increasing evidence shows that there is complex relationship between This article reviews latest research results mechanisms crosstalk in recent years, well their involvement neurodegenerative diseases, tumors other order provide ideas for treatment related diseases.

Language: Английский

Citations

13
Copper's dual role: Reviewing its impact on liver health and disease DOI
Tongtong Pan, Jiayin Huang, Xiaodong Wang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 152, P. 114391 - 114391

Published: March 12, 2025

Language: Английский

Citations

1
The Regulation of Trace Metal Elements in Cancer Ferroptosis DOI Creative Commons

Xiaoyan Wang,

Yuanyuan Xue, Lei Chang

et al.

Advanced Biology, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract Ferroptosis, as novel type of regulated cell death that has garnered widespread attention over the past decade, witnessed continuous discovery an increasing number regulatory mechanisms. Trace metal elements play a multifaceted and crucial role in oncology. Interestingly, it been increasingly evident these elements, such copper, are involved regulation iron accumulation, lipid peroxidation antiferroptotic systems, suggesting existence “nonferrous” mechanisms ferroptosis. In this review, comprehensive overview composition mechanism ferroptosis is provided. The interaction between copper metabolism (including cuproptosis) cancer, well roles other trace (such zinc, manganese, cobalt, molybdenum) specifically focused. Furthermore, applications nanomaterials based on metals cancer therapy also reviewed potential strategies for co‐targeting cuproptosis explored. Nevertheless, light intricate ambiguous nature interactions, ongoing research essential to further elucidate ferroptosis, thereby facilitating development therapeutic targets approaches treatment.

Language: Английский

Citations

1
Association of iron status with non-alcoholic fatty liver disease and liver fibrosis in US adults: a cross-sectional study from NHANES 2017–2018 DOI
Liao Tan,

Qiaoyu Zhou,

Jie Liu

et al.

Food & Function, Journal Year: 2023, Volume and Issue: 14(12), P. 5653 - 5662

Published: Jan. 1, 2023

Iron status indicators are closely associated with the occurrence of advanced liver fibrosis.

Language: Английский

Citations

20
Metabolic dysfunction: The silenced connection with fatty liver disease DOI Creative Commons
Mariana M. Ramírez-Mejía, Xingshun Qi, Ludovico Abenavoli

et al.

Annals of Hepatology, Journal Year: 2023, Volume and Issue: 28(6), P. 101138 - 101138

Published: July 18, 2023

Non-alcoholic fatty liver disease (NAFLD) represents a global public health burden. Despite the increase in its prevalence, has not received sufficient attention compared to associated diseases such as diabetes mellitus and obesity. In 2020 it was proposed rename NAFLD metabolic dysfunction-associated (MAFLD) order recognize risk factors complex pathophysiological mechanisms with development. Furthermore, along implementation of diagnostic criteria, aim is address whole clinical spectrum disease, regardless BMI presence other hepatic comorbidities. As would be expected paradigm shift, differing viewpoints have emerged regarding benefits disadvantages renaming disease. The following review aims describe way MAFLD from historical, perspective highlight why approach follow.

Language: Английский

Citations

20
Identification of Cuproptosis-Related Genes in Nonalcoholic Fatty Liver Disease DOI Open Access
Chutian Wu,

Xiongxiu Liu,

Lixian Zhong

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 18

Published: Feb. 21, 2023

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent hepatic pathology worldwide. However, precise molecular mechanisms for NAFLD are still not sufficiently explained. Recently, a new mode of cell death (cuproptosis) found. relationship between and cuproptosis remains unclear. We analyzed three public datasets (GSE89632, GSE130970, GSE135251) to identify cuproptosis-related genes stably expressed in NAFLD. Then, we performed series bioinformatics analyses explore genes. Finally, 6 high-fat diet- (HFD-) induced C57BL/6J mouse models were established carry out transcriptome analysis. The results gene set variation analysis (GSVA) revealed that pathway was abnormally activated certain degree (p = 0.035 GSE89632, p 0.016 0.22 GSE135251), principal component (PCA) showed group separated from control group, with first two components accounting 58.63%-74.88% variation. Among datasets, (DLD PDHB, < 0.01 or 0.001) upregulated Additionally, both DLD (AUC 0.786-0.856) PDHB 0.771-0.836) had favorable diagnostic properties, multivariate logistics regression model further improved properties 0.839-0.889). NADH, flavin adenine dinucleotide, glycine targeted DLD, pyruvic acid NADH DrugBank database. also associated clinical pathology, especially steatosis (DLD, 0.0013-0.025; 0.002-0.0026) activity score 0.004-0.02; 0.003-0.031). What more, correlated stromal R 0.38, 0.001; 0.31, immune 0.26, 0.27, Furthermore, Dld Pdhb significantly model. In conclusion, pathways, could be potential candidate therapeutic options.

Language: Английский

Citations

18
Unveiling the role of ferroptosis in the progression from NAFLD to NASH: recent advances in mechanistic understanding DOI Creative Commons

Qian Yu,

Lixing Song

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: July 4, 2024

Non-alcoholic fatty liver disease (NAFLD) is a prevalent and significant global public health issue. Nonalcoholic steatohepatitis (NASH) represents an advanced stage of NAFLD in terms pathology. However, the intricate mechanisms underlying progression from to NASH remain elusive. Ferroptosis, characterized by iron-dependent cell death distinguished other forms based on morphological, biochemical, genetic criteria, has emerged as potential participant with pivotal role driving progression. Nevertheless, its precise mechanism remains poorly elucidated. In this review article, we comprehensively summarize pathogenesis NAFLD/NASH ferroptosis while highlighting recent advances understanding mechanistic involvement NAFLD/NASH.

Language: Английский

Citations

7
Comparison of copper concentration between non-alcoholic fatty liver disease patients and normal individuals: A meta-analysis DOI Creative Commons
Yanfang Chen, Chutian Wu, Guanhong Li

et al.

Frontiers in Public Health, Journal Year: 2023, Volume and Issue: 11

Published: Feb. 1, 2023

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic worldwide. Copper metabolism plays an important role in pathogenesis of NAFLD. However, relationship between serum/hepatic copper concentration and NAFLD still debated. A literature search was performed using electronic databases to find publications up September 2022, where or ceruloplasmin evaluated. Finally, 6 articles with 9 unique outcomes involving 2,607 patients 1,441 non-NAFLD normal individuals were included. The pooled results showed that hepatic significantly decreased (SMD = −0.98, 95% CI [−1.21; −0.74], p &lt; 0.0001), sensitivity analysis also confirmed this. Nevertheless, serum −0.02, [−0.32; 0.28], 0.88) −0.03, [−0.69; 0.63], 0.93) not associated This meta-analysis revealed low found Larger cohort studies related trials are needed further validate result this future.

Language: Английский

Citations

14
Insights into the liver-eyes connections, from epidemiological, mechanical studies to clinical translation DOI Creative Commons
Junhao Wu, Caihan Duan,

Yuanfan Yang

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 10, 2023

Abstract Maintenance of internal homeostasis is a sophisticated process, during which almost all organs get involved. Liver plays central role in metabolism and involves endocrine, immunity, detoxification storage, therefore it communicates with distant through such mechanisms to regulate pathophysiological processes. Dysfunctional liver often accompanied by pathological phenotypes organs, including the eyes. Many reviews have focused on crosstalk between gut, brain, heart, kidney, but no attention paid In this review, we summarized intimate connections eyes from three aspects. Epidemiologically, suggest liver-related, potential, protective risk factors for typical eye disease as well indicators connected status. For molecular mechanism aspect, elaborate their inter-organ (glucose, lipid, proteins, vitamin, mineral), (ammonia bilirubin), immunity (complement inflammation regulation) aspect. clinical application part, emphasize latest advances utilizing liver-eye axis diagnosis therapy, involving artificial intelligence-deep learning-based novel diagnostic tools detecting adeno-associated viral vector-based gene therapy method curing blinding disease. We aim focus provide insights into communications help resolve existed clinically significant issues.

Language: Английский

Citations

14