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共17篇 平均IF=13.6 (4.9-51)更多分析
  • 1区Q1影响因子: 13.6
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    1. TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase.
    1. TRIM56 通过促进脂肪酸合酶的降解来预防非酒精性脂肪肝。
    期刊:The Journal of clinical investigation
    日期:2024-01-11
    DOI :10.1172/JCI166149
    Nonalcoholic fatty liver disease (NAFLD) encompasses a disease continuum from simple steatosis to nonalcoholic steatohepatitis (NASH). However, there are currently no approved pharmacotherapies for NAFLD, although several drugs are in advanced stages of clinical development. Because of the complex pathophysiology and heterogeneity of NAFLD, the identification of potential therapeutic targets is clinically important. Here, we demonstrated that tripartite motif 56 (TRIM56) protein abundance was markedly downregulated in the livers of individuals with NAFLD and of mice fed a high-fat diet. Hepatocyte-specific ablation of TRIM56 exacerbated the progression of NAFLD, while hepatic TRIM56 overexpression suppressed it. Integrative analyses of interactome and transcriptome profiling revealed a pivotal role of TRIM56 in lipid metabolism and identified the lipogenesis factor fatty acid synthase (FASN) as a direct binding partner of TRIM56. TRIM56 directly interacted with FASN and triggered its K48-linked ubiquitination-dependent degradation. Finally, using artificial intelligence-based virtual screening, we discovered an orally bioavailable small-molecule inhibitor of FASN (named FASstatin) that potentiates TRIM56-mediated FASN ubiquitination. Therapeutic administration of FASstatin improved NAFLD and NASH pathologies in mice with an optimal safety, tolerability, and pharmacokinetics profile. Our findings provide proof of concept that targeting the TRIM56/FASN axis in hepatocytes may offer potential therapeutic avenues to treat NAFLD.
  • 3区Q1影响因子: 4.9
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    2. Understanding the Relationship between Nonalcoholic Fatty Liver Disease and Thyroid Disease.
    2. 了解非酒精性脂肪性肝病与甲状腺疾病的关系。
    期刊:International journal of molecular sciences
    日期:2023-09-27
    DOI :10.3390/ijms241914605
    The prevalence of hypothyroidism in patients with nonalcoholic fatty liver disease (NAFLD) is high (22.4%). Thyroid hormones (THs) regulate many metabolic activities in the liver by promoting the export and oxidation of lipids, as well as de novo lipogenesis. They also control hepatic insulin sensitivity and suppress hepatic gluconeogenesis. Because of its importance in lipid and carbohydrate metabolism, the involvement of thyroid dysfunction in the pathogenesis of NAFLD seems plausible. The mechanisms implicated in this relationship include high thyroid-stimulating hormone (TSH) levels, low TH levels, and chronic inflammation. The activity of the TH receptor (THR)-β in response to THs is essential in the pathogenesis of hypothyroidism-induced NAFLD. Therefore, an orally active selective liver THR-β agonist, Resmetirom (MGL-3196), was developed, and has been shown to reduce liver fat content, and as a secondary end point, to improve nonalcoholic steatohepatitis. The treatment of NAFLD with THR-β agonists seems quite promising, and other agonists are currently under development and investigation. This review aims to shine a light on the pathophysiological and epidemiological evidence regarding this relationship and the effect that treatment with THs and selective liver THR-β agonists have on hepatic lipid metabolism.
  • 1区Q1影响因子: 51
    3. Lifestyle interventions in nonalcoholic fatty liver disease.
    3. 生活方式干预非酒精性脂肪肝病。
    期刊:Nature reviews. Gastroenterology & hepatology
    日期:2023-07-04
    DOI :10.1038/s41575-023-00800-4
    Nonalcoholic fatty liver disease (NAFLD) is a dynamic chronic liver disease that develops in close association with metabolic irregularities. Between 2016 and 2019, the global prevalence among adults was reported as 38% and among children and adolescents it was about 10%. NAFLD can be progressive and is associated with increased mortality from cardiovascular disease, extrahepatic cancers and liver complications. Despite these numerous adverse outcomes, no pharmacological treatments currently exist to treat nonalcoholic steatohepatitis, the progressive form of NAFLD. Therefore, the main treatment is the pursuit of a healthy lifestyle for both children and adults, which includes a diet rich in fruits, nuts, seeds, whole grains, fish and chicken and avoiding overconsumption of ultra-processed food, red meat, sugar-sweetened beverages and foods cooked at high heat. Physical activity at a level where one can talk but not sing is also recommended, including leisure-time activities and structured exercise. Avoidance of smoking and alcohol is also recommended. Policy-makers, community and school leaders need to work together to make their environments healthy by developing walkable and safe spaces with food stores stocked with culturally appropriate and healthy food items at affordable prices as well as providing age-appropriate and safe play areas in both schools and neighbourhoods.
  • 1区Q1影响因子: 12.6
    4. N-methyladenosine RNA modification in nonalcoholic fatty liver disease.
    4. 非酒精性脂肪性肝病中的 N - 甲基腺苷 RNA 修饰.
    期刊:Trends in endocrinology and metabolism: TEM
    日期:2023-09-25
    DOI :10.1016/j.tem.2023.09.002
    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, influencing numerous regulatory axes and extrahepatic vital organs. The molecular mechanisms that lead to the progression of NAFLD remain unclear and knowledge on the pathways causing hepatocellular damage followed by lipid accumulation is limited. Recently, a number of studies have shown that mRNA N-methyladenosine (m6A) modification contributes to the progression of NAFLD. In this review, we summarize current knowledge on m6A modification in the metabolic processes associated with NAFLD and discuss the challenges of and prospects for therapeutic avenues based on m6A regulation for the treatment of liver disease.
  • 1区Q1影响因子: 12.9
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    5. MicroRNA regulation of AMPK in nonalcoholic fatty liver disease.
    5. AMPK在非酒精性脂肪肝中的微小RNA调节。
    期刊:Experimental & molecular medicine
    日期:2023-09-01
    DOI :10.1038/s12276-023-01072-3
    Obesity-associated nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is the leading cause of liver failure and death. The function of AMP-activated protein kinase (AMPK), a master energy sensor, is aberrantly reduced in NAFLD, but the underlying mechanisms are not fully understood. Increasing evidence indicates that aberrantly expressed microRNAs (miRs) are associated with impaired AMPK function in obesity and NAFLD. In this review, we discuss the emerging evidence that miRs have a role in reducing AMPK activity in NAFLD and nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. We also discuss the underlying mechanisms of the aberrant expression of miRs that can negatively impact AMPK, as well as the therapeutic potential of targeting the miR-AMPK pathway for NAFLD/NASH.
  • 1区Q1影响因子: 6.2
    6. Corn Oligopeptide Alleviates Nonalcoholic Fatty Liver Disease by Regulating the Sirtuin Signaling Pathway.
    6. 玉米寡肽通过调节 Sirtuin 信号通路缓解非酒精性脂肪肝.
    期刊:Journal of agricultural and food chemistry
    日期:2024-03-15
    DOI :10.1021/acs.jafc.3c09058
    Nonalcoholic fatty liver disease (NAFLD) represents the most prevalent type of chronic liver disease, spanning from simple steatosis to nonalcoholic steatohepatitis (NASH). Corn oligopeptide (CP) is a functional peptide known for its diverse pharmacological effects on metabolism. In this study, we evaluated the protective activity of CP against fatty liver disease. Oral administration of CP significantly reduced body weight gain by 2.95%, serum cholesterol by 22.54%, and liver injury, as evidenced by a reduction of 32.19% in serum aspartate aminotransferase (AST) and 49.10% in alanine aminotransferase (ALT) levels in mice subjected to a high-fat diet (HFD). In a streptozotocin/HFD-induced NASH mouse model, CP attenuated body weight gain by 5.11%, liver injury (with a 34.15% decrease in AST and 11.43% decrease in ALT), and, to some extent, liver inflammation and fibrosis. Proteomic analysis revealed the modulation of oxidative phosphorylation and sirtuin (SIRT) signaling pathways by CP. Remarkably, CP selectively inhibited the hepatic expression of mitochondrial SIRT3 and SIRT5 in both HFD and NASH models. In summary, CP demonstrates a preventive effect against metabolic-stress-induced NAFLD progression by modulating oxidative stress and the SIRT signaling pathway, suggesting the potential of CP as a therapeutic agent for the treatment of NAFLD and advanced-stage NASH.
  • 2区Q1影响因子: 5.6
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    7. Pharmacological potential of ginseng and ginsenosides in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.
    7. 人参和人参皂苷在非酒精性脂肪肝和非酒精性脂肪性肝炎中的药理潜力。
    期刊:Journal of ginseng research
    日期:2023-11-14
    DOI :10.1016/j.jgr.2023.11.003
    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic fat accumulation, while nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD characterized by hepatic inflammation, fibrosis, and liver injury, resulting in liver cirrhosis and hepatocellular carcinoma (HCC). Given the evidence that ginseng and its major bioactive components, ginsenosides, have potent anti-adipogenic, anti-inflammatory, anti-oxidative, and anti-fibrogenic effects, the pharmacological effect of ginseng and ginsenosides on NAFLD and NASH is noteworthy. Furthermore, numerous studies have successfully demonstrated the protective effect of ginseng on these diseases, as well as the underlying mechanisms in animal disease models and cells, such as hepatocytes and macrophages. This review discusses recent studies that explore the pharmacological roles of ginseng and ginsenosides in NAFLD and NASH and highlights their potential as agents to prevent and treat NAFLD, NASH, and liver diseases caused by hepatic steatosis and inflammation.
  • 1区Q1影响因子: 11
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    8. Fungal signature differentiates alcohol-associated liver disease from nonalcoholic fatty liver disease.
    8. 真菌特征将酒精相关性肝病与非酒精性脂肪性肝病区分开来.
    期刊:Gut microbes
    日期:2024-02-01
    DOI :10.1080/19490976.2024.2307586
    The fungal microbiota plays an important role in the pathogenesis of alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to compare changes of the fecal fungal microbiota between patients with ALD and NAFLD and to elucidate patterns in different disease stages between the two conditions. We analyzed fungal internal transcribed spacer 2 (ITS2) sequencing using fecal samples from a cohort of 48 patients with ALD, 78 patients with NAFLD, and 34 controls. The fungal microbiota differed significantly between ALD and NAFLD. The genera , , , and the species (), (), () were significantly increased in patients with ALD, whereas the genera and were significantly increased in the NAFLD cohort. We identified the fungal signature consisting of , , , and to have the highest discriminative ability to detect ALD vs NAFLD with an area under the curve (AUC) of 0.93. When stratifying the ALD and NAFLD cohorts by fibrosis severity, the fungal signature with the highest AUC of 0.92 to distinguish ALD F0-F1 vs NAFLD F0-F1 comprised , , , , and . For more advanced fibrosis stages (F2-F4), the fungal signature composed of , , , and achieved the highest AUC of 0.99 to differentiate ALD from NAFLD. This is the first study to identify a fungal signature to differentiate two metabolic fatty liver diseases from each other, specifically ALD from NAFLD. This might have clinical utility in unclear cases and might hence help shape treatment approaches. However, larger studies are required to validate this fungal signature in other populations of ALD and NAFLD.
  • 2区Q1影响因子: 5.9
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    9. Macrophage metabolism in nonalcoholic fatty liver disease.
    9. 非酒精性脂肪性肝病的巨噬细胞代谢.
    期刊:Frontiers in immunology
    日期:2023-10-04
    DOI :10.3389/fimmu.2023.1257596
    Nonalcoholic fatty liver disease (NAFLD) and its inflammatory and often progressive subtype nonalcoholic steatohepatitis (NASH), have emerged as significant contributors to hepatic morbidity worldwide. The pathophysiology of NAFLD/NASH is multifaceted, variable, and remains incompletely understood. The pivotal role of liver-resident and recruited macrophages in the pathogenesis of NAFLD and NASH is widely acknowledged as a crucial factor in innate immunity. The remarkable plasticity of macrophages enables them to assume diverse activation and polarization states, dictated by their immunometabolism microenvironment and functional requirements. Recent studies in the field of immunometabolism have elucidated that alterations in the metabolic profile of macrophages can profoundly influence their activation state and functionality, thereby influencing various pathological processes. This review primarily focuses on elucidating the polarization and activation states of macrophages, highlighting the correlation between their metabolic characteristics and the transition from pro-inflammatory to anti-inflammatory phenotypes. Additionally, we explore the potential of targeting macrophage metabolism as a promising therapeutic approach for the management of NAFLD/NASH.
  • 3区Q1影响因子: 4.9
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    10. Innovative Molecular Targets and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 3.0.
    10. 非酒精性脂肪性肝病 / 非酒精性脂肪性肝炎 ( NAFLD / NASH ) 3.0 的创新分子靶点和治疗方法。
    期刊:International journal of molecular sciences
    日期:2024-04-03
    DOI :10.3390/ijms25074010
    The aim of this Special Issue is to provide an update on the diagnosis and treatment of nonalcoholic fatty liver disease (NAFLD), which is the most prevalent liver disease worldwide; however, there are still no specific treatment agents [...].
  • 1区Q1影响因子: 51
    11. Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology.
    11. 肝细胞癌的监测,利用障碍,改变的病因学的影响。
    期刊:Nature reviews. Gastroenterology & hepatology
    日期:2023-08-03
    DOI :10.1038/s41575-023-00818-8
    Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of α-fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity. In this Review, we discuss the current status of HCC surveillance and the remaining challenges, including the changing aetiology of liver disease. We also discuss strategies to improve the utilization and quality of surveillance for HCC.
  • 1区Q1影响因子: 51
    12. The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease.
    12. 酒精肝病之间的交叉和非酒精性脂肪肝病。
    期刊:Nature reviews. Gastroenterology & hepatology
    日期:2023-08-15
    DOI :10.1038/s41575-023-00822-y
    Nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) are the leading causes of chronic liver disease worldwide. NAFLD and ALD share pathophysiological, histological and genetic features and both alcohol and metabolic dysfunction coexist as aetiological factors in many patients with hepatic steatosis. A diagnosis of NAFLD requires the exclusion of significant alcohol consumption and other causes of liver disease. However, data suggest that significant alcohol consumption is often under-reported in patients classified as having NAFLD and that alcohol and metabolic factors interact to exacerbate the progression of liver disease. In this Review, we analyse existing data on the interaction between alcohol consumption and metabolic syndrome as well as the overlapping features and differences in the pathogenesis of ALD and NAFLD. We also discuss the clinical implications of the coexistence of alcohol consumption, of any degree, in patients with evidence of metabolic derangement as well as the use of alcohol biomarkers to detect alcohol intake. Finally, we summarize the evolving nomenclature of fatty liver disease and describe a recent proposal to classify patients at the intersection of NAFLD and ALD. We propose that, regardless of the presumed aetiology, patients with fatty liver disease should be evaluated for both metabolic syndrome and alcohol consumption to enable better prognostication and a personalized medicine approach.
  • 1区Q1影响因子: 51
    13. Cellular stress in the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis.
    13. 细胞压力在非酒精 s肝炎和肝纤维化疾病的发病中.
    期刊:Nature reviews. Gastroenterology & hepatology
    日期:2023-09-07
    DOI :10.1038/s41575-023-00832-w
    The burden of chronic liver disease is rising substantially worldwide. Fibrosis, characterized by excessive deposition of extracellular matrix proteins, is the common pathway leading to cirrhosis, and limited treatment options are available. There is increasing evidence suggesting the role of cellular stress responses contributing to fibrogenesis. This Review provides an overview of studies that analyse the role of cellular stress in different cell types involved in fibrogenesis, including hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells and macrophages.
  • 1区Q1影响因子: 51
    14. Digital pathology for nonalcoholic steatohepatitis assessment.
    14. 非酒精性脂肪性肝炎评估的数字病理学。
    期刊:Nature reviews. Gastroenterology & hepatology
    日期:2023-10-03
    DOI :10.1038/s41575-023-00843-7
    Histological assessment of nonalcoholic fatty liver disease (NAFLD) has anchored knowledge development about the phenotypes of the condition, their natural history and their clinical course. This fact has led to the use of histological assessment as a reference standard for the evaluation of efficacy of drug interventions for nonalcoholic steatohepatitis (NASH) - the more histologically active form of NAFLD. However, certain limitations of conventional histological assessment systems pose challenges in drug development. These limitations have spurred intense scientific and commercial development of machine learning and digital approaches towards the assessment of liver histology in patients with NAFLD. This research field remains an area in rapid evolution. In this Perspective article, we summarize the current conventional assessment of NASH and its limitations, the use of specific digital approaches for histological assessment, and their application to the study of NASH and its response to therapy. Although this is not a comprehensive review, the leading tools currently used to assess therapeutic efficacy in drug development are specifically discussed. The potential translation of these approaches to support routine clinical assessment of NAFLD and an agenda for future research are also discussed.
  • 1区Q1影响因子: 51
    15. Recompensation in cirrhosis: unravelling the evolving natural history of nonalcoholic fatty liver disease.
    15. 肝硬化的代偿 : 揭示非酒精性脂肪肝疾病不断发展的自然史。
    期刊:Nature reviews. Gastroenterology & hepatology
    日期:2023-10-05
    DOI :10.1038/s41575-023-00846-4
    Recompensation has gained increasing attention in the field of cirrhosis, particularly in chronic liver disease with a definite aetiology. The current global prevalence of obesity and nonalcoholic fatty liver disease (NAFLD) is increasing, but there is currently a lack of a clear definition for recompensation in NAFLD-related cirrhosis. Here, we provide an up-to-date perspective on the natural history of NAFLD, emphasizing the reversible nature of the disease, summarizing possible mechanisms underlying recompensation in NAFLD, discussing challenges that need to be addressed and outlining future research directions in the field. Recompensation is a promising goal in patients with NAFLD-related cirrhosis, and further studies are needed to explore its underlying mechanisms and uncover its clinical features.
  • 1区Q1影响因子: 33
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    16. Artificial intelligence-assisted digital pathology for non-alcoholic steatohepatitis: current status and future directions.
    16. 人工智能辅助数字病理学治疗非酒精性脂肪性肝炎 : 现状和未来方向。
    期刊:Journal of hepatology
    日期:2023-10-24
    DOI :10.1016/j.jhep.2023.10.015
    The worldwide prevalence of non-alcoholic steatohepatitis (NASH) is increasing, causing a significant medical burden, but no approved therapeutics are currently available. NASH drug development requires histological analysis of liver biopsies by expert pathologists for trial enrolment and efficacy assessment, which can be hindered by multiple issues including sample heterogeneity, inter-reader and intra-reader variability, and ordinal scoring systems. Consequently, there is a high unmet need for accurate, reproducible, quantitative, and automated methods to assist pathologists with histological analysis to improve the precision around treatment and efficacy assessment. Digital pathology (DP) workflows in combination with artificial intelligence (AI) have been established in other areas of medicine and are being actively investigated in NASH to assist pathologists in the evaluation and scoring of NASH histology. DP/AI models can be used to automatically detect, localise, quantify, and score histological parameters and have the potential to reduce the impact of scoring variability in NASH clinical trials. This narrative review provides an overview of DP/AI tools in development for NASH, highlights key regulatory considerations, and discusses how these advances may impact the future of NASH clinical management and drug development. This should be a high priority in the NASH field, particularly to improve the development of safe and effective therapeutics.
  • 1区Q1影响因子: 33
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    17. Pharmacologic inhibition of lipogenesis for the treatment of NAFLD.
    17. 用于治疗 NAFLD 的脂肪生成的药理学抑制。
    期刊:Journal of hepatology
    日期:2023-11-15
    DOI :10.1016/j.jhep.2023.10.042
    The hepatic accumulation of excess triglycerides is a seminal event in the initiation and progression of non-alcoholic fatty liver disease (NAFLD). Hepatic steatosis occurs when the hepatic accrual of fatty acids from the plasma and de novo lipogenesis (DNL) is no longer balanced by rates of fatty acid oxidation and secretion of very low-density lipoprotein-triglycerides. Accumulating data indicate that increased rates of DNL are central to the development of hepatic steatosis in NAFLD. Whereas the main drivers in NAFLD are transcriptional, owing to both hyperinsulinemia and hyperglycaemia, the effectors of DNL are a series of well-characterised enzymes. Several have proven amenable to pharmacologic inhibition or oligonucleotide-mediated knockdown, with lead compounds showing liver fat-lowering efficacy in phase II clinical trials. In humans with NAFLD, percent reductions in liver fat have closely mirrored percent inhibition of DNL, thereby affirming the critical contributions of DNL to NAFLD pathogenesis. The safety profiles of these compounds have so far been encouraging. It is anticipated that inhibitors of DNL, when administered alone or in combination with other therapeutic agents, will become important agents in the management of human NAFLD.
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