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Purpose: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. This study focused on assessing the predictive significance of NAFLD for recurrent stroke and transient ischemic attack (TIA) risk to determine the value of NAFLD., Method: This study included 742 participants (mean age: 64.26 ± 9.42 years, 497 males) with carotid atherosclerosis who underwent carotid CT angiography (CTA) between January 2013 and December 2021 in this retrospective study. NAFLD was diagnosed by non-enhanced abdominal CT. The clinical endpoint was a recurrent ischemic stroke or TIA. Cox proportional hazards and Kaplan-Meier analysis assessed whether NAFLD was associated with the endpoint. We accessed the predictive values of NAFLD, clinical, plaque characteristics, and combined model by the C statistics. The predictive performance of the combined model was assessed by receiver operating characteristic curve (ROC) analysis., Results: A total of 742 participants (mean age: 64.26 ± 9.42 years, 497 males) were included. During 2.9 years of follow-up (interquartile range, 2.1-3.9), 166 patients reached the clinical endpoint. Multivariable cox analyses showed NAFLD was associated with recurrent stroke or TIA in all groups (all P<0.05). Patients with NAFLD had a lower event-free survival (EFS) rate than those without NAFLD (P<0.05). The combined model, including NAFLD, clinical data and plaque features, showed the best performance in predicting the clinical endpoint (AUC=0.79)., Conclusions: NAFLD contributes to the prediction of recurrent ischemic stroke or TIA. NAFLD may be a novel imaging marker that offers a new perspective on preventing cardiovascular disease in the clinic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To evaluate the diagnostic value of the FibroScan-AST (FAST) score, non-alcoholic fatty liver fibrosis score (NFS), FibroScan, and liver fibrosis index (FIB-4) for identifying fibrotic non-alcoholic steatohepatitis (NASH) in patients with chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD)., Methods: All patients with CHB and MAFLD who underwent liver biopsy at the Zhenjiang Third Hospital affiliated with Jiangsu University between August 2010 and December 2022 were included in the analysis. The diagnostic accuracy of FAST, NFS, FibroScan, and FIB-4 for diagnosing NASH and liver fibrosis were evaluated based on the area under the receiver-operating characteristic curve (AUC)., Results: A total of 156 patients with CHB combined with MAFLD were included, including 69 with NASH and fibrosis stage 2 or higher (NASH+ F  ≥ 2), and 16 with NASH and cirrhosis (NASH+F4). The AUC of FAST, NFS, liver stiffness measurement (LSM), and FIB-4 for diagnosing NASH+ F  ≥ 2 was 0.739 ( p  < 0.001), 0.643 ( p  = 0.006), 0.754 ( p  < 0.001), and 0.665 ( p  = 0.003), respectively. The specificity of FAST, NFS, LSM, and FIB-4 was 67%, 51.8%, 78.6% and 76.8%, respectively, and the sensitivity was 75%, 78.6%, 67.9%, and 53.6%, respectively. No significant differences were found between groups. The AUC of FAST, NFS, LSM, and FIB-4 for diagnosing NASH+F4 was 0.650 ( p  = 0.038), 0.725 ( p  = 0.001), 0.851 ( p  < 0.001), and 0.560 ( p  = 0.533), respectively. The specificity of the FAST, NFS, LSM, and FIB-4 was 55.9%, 50.0%, 71.6%, and 75.5%, respectively and the sensitivity was 80.0%, 100%, 100%, and 50.0%, respectively. The differences between AUCs of FIB-4 and FAST compared with LSM were 0.291 and 0.201, respectively ( p  < 0.05)., Conclusion: In patients with CHB combined with MAFLD, FAST did not have better accuracy than NFS and FIB-4 for predicting fibrotic NASH, whereas LSM had better accuracy than FAST and FIB-4.

Non-alcoholic fatty liver disease (NAFLD) is a progressive condition, advancing from simple hepatic lipid accumulation to inflammation, fibrosis, and increased risk of mortality. This study explores the therapeutic efficacy of bioactive peptides PIISVYWK (P1) and FSVVPSPK (P2) in ameliorating NAFLD in both oleic acid-treated HepG2 cells and high-fat diet (HFD)-induced mice. Our findings demonstrated that P1 and P2 significantly reduced hepatic fat deposition, enhanced lipolysis by promoting the release of free glycerol and free fatty acids, and suppressed key de novo lipogenesis-related proteins, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1 (SREBP-1), and fatty acid synthase (FAS). Furthermore, both peptides stimulated fatty acid oxidation via phosphorylation of AMP-activated protein kinase (AMPK) and hormone-sensitive lipase (HSL). Notably, reductions in body and liver weight, along with improved cholesterol profiles and liver function markers (alanine transaminase and aspartate aminotransferase), were observed in HFD mice. Additionally, P1 and P2 significantly attenuated the production of pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in both in vitro and in vivo models. Collectively, these results highlight the potent therapeutic potential of P1 and P2 in mitigating NAFLD progression, offering a promising intervention for this increasingly prevalent metabolic disorder., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease globally, with a complex and contentious pathogenesis. Caveolin-1 (CAV1) is an important regulator of liver function and can mitigate liver injury by scavenging reactive oxygen species (ROS). Evidence suggests that NOX4 is a source of ROS production, that oxidative stress and ferroptosis are closely related, and that both are involved in the onset and progression of NAFLD. However, whether CAV1 attenuates liver injury in NAFLD caused by high-fat diet via the NOX4/ROS/GPX4 pathway remains unclear. An in vivo fatty liver model was established by feeding mice with a high-fat diet for 16 weeks. In addition, an in vitro fatty liver model was established by incubating AML-12 cells with free fatty acids for 24 h using an in vitro culture method. In our study, it was observed that a high-fat diet induces mitochondrial damage and worsens oxidative stress in NAFLD. This diet also hinders GPX4 expression, leading to an escalation of ferroptosis and lipid accumulation. To counteract these effects, intraperitoneal administration of CSD peptide in mice attenuated the high-fat diet-induced liver mitochondrial damage and ferroptosis. Likewise, overexpression of CAV1 resulted in an increase in GPX4 expression and a reduction in levels of ROS-mediated iron metamorphosis, thus mitigating the progression of the disease. However, the effects of CAV1 on GPX4-mediated ferroptosis and lipid deposition could be reversed by CAV1 small interfering RNA (SiRNA). Finally, NOX4 inhibitor (GLX351322) treatment increased CAV1 siRNA-mediated GPX4 expression and decreased the level of ROS-mediated ferroptosis. These findings suggest a potential mechanism underlying the protective role of CAV1 against high-fat diet-induced hepatotoxicity in NAFLD, shedding new light on the interplay between CAV1, GPX4, and ferroptosis in liver pathology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. The mechanism by which bisphenol A (BPA) promots NAFLD remains unclear. Palmitic acid (PA) and lipopolysaccharide (LPS) were used to simulate NAFLD in HepG2 cells in vitro . Total cholesterol (TC), triglyceride (TG) content, and lipid accumulation were measured to evaluate lipid metabolism. The caspase-1-stained cells and NLRP3 inflammasome-associated proteins were evaluated for pyroptosis. Western blot analysis was used to detect protein levels and co-immunoprecipitation (Co-IP) was used to detect the association between the proteins. Cycloheximide (CHX) treatment combined with western blot was performed to access protein stability. This data have shown that BPA induces lipid metabolism dysfunction and pyroptosis by upregulating O-GlcNAc transferase (OGT) level. NLRP3 directly interacts with OGT, and elevated OGT enhanced the stability of NLRP3 protein. BPA promoted OGT-mediated O-GlcNAcylation to stabilised NLRP3, thus accelerating NAFLD progress in vitro . Our study reveals that BPA, as an environmental factor, may be involved in the promotion of NAFLD, and that targeting NLRP3 and OGT may inhibit BPA's induction of NAFLD.

Objective: The objective of this study was to thoroughly investigate the clinical value of triglyceride glucose-body mass index (TyG-BMI) in patients diagnosed with non-alcoholic fatty liver disease (NAFLD). Specifically, we aimed to determine its association with non-alcoholic steatohepatitis (NASH) and the progression of liver fibrosis., Methods: The study included 393 patients diagnosed with NAFLD after liver biopsy. The patients were divided into two distinct cohorts: a training cohort ( N  = 320) and a validation cohort ( N  = 73). The training cohort was further divided into four groups based on TyG-BMI quartiles. The clinical characteristics of the patients in each group were compared in detail, and the association between TyG-BMI and NASH, NAFLD Activity Score (NAS) ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis was analyzed using multiple models. Additionally, we generated receiver operating characteristic (ROC) curves to evaluate the predictive ability of TyG-BMI for NASH and fibrosis staging in patients with NAFLD., Results: Patients with higher TyG-BMI values had a significantly higher prevalence of NASH, NAS ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis (all p  < .05). TyG-BMI was an independent predictor of these diseases in both unadjusted and adjusted models (all p  < .05). ROC curve analysis further revealed the excellent performance of TyG-BMI in predicting NASH, NAS ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis. The validation cohort yielded analogous results. Furthermore, we constructed three multivariate models of TyG-BMI in conjunction with elastography metrics, which demonstrated elevated diagnostic AUC values of 0.782, 0.792, 0.794, 0.785, 0.834, and 0.845, respectively., Conclusion: This study confirms a significant association between insulin resistance and NAFLD, including at-risk NASH and fibrosis staging, as assessed using the TyG-BMI index. TyG-BMI and its associated multivariate models can be valuable noninvasive indicators for NAFLD diagnosis, risk stratification, and disease course monitoring.

Background: Non-alcoholic fatty liver disease (NAFLD) is a metabolically stressed liver injury closely related to insulin resistance and genetic susceptibility and has become the leading chronic liver disease in China., Purpose: To analyze the effectiveness of five Chinese patent medicines used alone or in combination with western medications (WM) for NAFLD using Bayesian network meta-analysis., Methods: Searches were conducted in Embase, Cochrane Library, PubMed, CNKI, Wanfang Database, VIP, and SinoMed for randomized controlled trials (RCTs) on Danning tablets, Huazhi Rougan granules, Dangfei Liganning capsules, Kezhi capsules, and Qianggan capsules, either alone or in combination with WM for NAFLD, up to January 10, 2024. This study was screened based on pre-designed inclusion and exclusion criteria, and the risk of bias was evaluated using the Cochrane ROB2 tool. The primary outcome was clinical efficacy rate, while secondary outcomes included levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Triglycerides (TG), and Low-density lipoprotein cholesterol (LDL-C). These data will be analyzed using WinBUGS 1.4.3 and then visualized using Stata 14.0 software., Results: A total of 77 RCTs involving 7770 patients were included. The results indicated that Huazhi Rougan granules combined with WM (OR = 0.13, 95 % CI 0.05 ∼ 0.26) had a SUCRA probability value of 81.7 %, ranked first in clinical efficacy and significantly improved blood lipids levels including TG, High-density Lipoprotein Cholesterol (HDL-C), and LDL-C, Total cholesterol (TC). For the Chinese patent medicines alone, Danning tablets led with a 75.3 % clinical efficacy rate. Huazhi Rougan granules significantly increased levels of ALT (96.2 %) and AST (MD = -14.48, 95 % CI -23.38 ∼ -5.32). Dangfei Liganning capsules demonstrated significant efficacy in improving TG (73.1 %) and TC (83 %) levels., Conclusion: In the treatment of NAFLD, the combination of Huazhi Rougan granules and WM demonstrated significant clinical effectiveness and improvement in blood lipid profiles. For different outcome indicators, Danning tablets used alone showed the highest clinical efficacy, while significant improvement in liver function indicators was best achieved with Huazhi Rugan granules used alone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

The Angiopoietin-like 4 (ANGPTL4) and ETS Variant Transcription Factor 4 (ETV4) are involved in the metabolic transition and carcinogenesis in the liver. However, the role of ETV4 in the development of non-alcoholic fatty liver disease (NAFLD) is currently unknown. Our study reveals that ETV4 expression was upregulated in the diet-induced non-alcoholic fatty liver disease, and plays a critical role in the dysregulated lipid metabolism. We demonstrate a mechanism by which ANGPTL4 regulates lipid homeostasis via involving the AMPK/ETV4 axis. Transient knockdown of ETV4 abolished the ANGPTL4-induced expression of Srebp1c, Acc and Fasn. Insulin treatment potentially increased the physical association of ETV4 with SREBP1, and promotes nuclear translocation and transcriptional activity of SREBP1. In addition, we show that combined therapy with omega-3 fatty acids and diacylglycerol O-acyltransferase inhibitor 1 (DGAT1) inhibitor (A-922500) counteracted the ANGPTL4-ETV4 axis-induced lipogenesis in vitro, and in vivo in obese mice via activation of GPR120-βarrestin2-AMPK pathway. Finally, we demonstrate that targeted pharmacologic therapy using GalNac-ETV4 siRNA that specifically inhibits ETV4 gene expression in the liver protects against diet-induced NAFLD, obesity and dyslipidemia. Hence, our study reveal previously unrecognized role of ETV4 in the NAFLD, and provides rationale targeting ETV4 to treat NAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Heart failure (HF) and non-alcoholic fatty liver disease (NAFLD) are significant global health issues with a complex interrelationship. This study investigates their shared biomarkers and causal relationships using bioinformatics and Mendelian randomization (MR) approaches., Methods: We analysed NAFLD and HF datasets from the Gene Expression Omnibus (GEO). The GSE126848 dataset included 57 liver biopsy samples [14 healthy individuals, 12 obese subjects, 15 NAFL patients and 16 non-alcoholic steatohepatitis (NASH) patients]. The GSE24807 dataset comprised 12 NASH samples and 5 healthy controls. The GSE57338 dataset included 313 cardiac muscle samples [177 HF patients (95 ischaemic heart disease patients and 82 idiopathic dilated cardiomyopathy patients) and 136 healthy controls]. The GSE84796 dataset consisted of 10 end-stage HF patients and 7 healthy hearts procured from organ donors. We identified differentially expressed genes (DEGs) and constructed a protein-protein interaction (PPI) network. Functional pathways were elucidated through enrichment analyses using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneMANIA annotation. Single nucleotide polymorphism (SNP) data for HF and NAFLD were sourced from genome-wide association studies (GWAS). The HF dataset included 486 160 samples (14 262 experimental and 471 898 control), and the NAFLD dataset comprised 377 988 samples (4761 experimental and 373 227 control). MR analysis investigates the causal interrelations., Results: Our analysis revealed 4032 DEGs from GSE126848 and 286 DEGs from GSE57338. The top 10 hub genes (CD163, VSIG4, CXCL10, FCER1G, FPR1, C1QB, CCR1, C1orf162, MRC1 and CD38) were significantly enriched in immune response, calcium ion concentration regulation and positive regulation of monocyte chemotaxis. CIBERSORT analysis indicated associations between these hub genes and natural killer (NK) cells and macrophages. Transcription factor (TF) target prediction for CD38, CXCL10 and CCR1 highlighted related TFs. A two-sample MR analysis confirmed a bidirectional causal relationship between NAFLD and HF. The main method [inverse variance weighted (IVW)] demonstrated a significant positive causal relationship between NAFLD and HF [P = 0.037; odds ratio (OR) = 1.024; 95% confidence interval (CI): 1.001 to 1.048]. Similarly, HF was associated with an increase in the risk of NAFLD (P < 0.001; OR = 1.117; 95% CI: 1.053 to 1.185)., Conclusions: Our findings reveal novel molecular signatures common to NAFLD and HF and confirm their bidirectional causality, highlighting the potential for targeted therapeutic interventions and prompting further investigation into their intricate relationship., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Non-alcoholic fatty liver disease (NAFLD), a prevalent chronic liver disease, is marked by excessive lipid deposition in the liver without alcohol abuse. Scapharca subcrenatum, a major Chinese farmed bivalve, yields S. subcrenatum polysaccharide (TGP), an active substance with known biological activity. Previous studies revealed TGP's significant regulatory effect on a high-fat diet (HFD)-induced NAFLD in mice. However, the precise mechanisms, particularly involving gut microbiota, remain unclear. In the current study, an antibiotic-treated mouse model was established to determine the mechanistic role of the gut microbiota in the observed anti-obesity effects of TGP. In addition, 16S rRNA genomic and metagenome-derived taxonomic analyses were performed to assess the gut microbial populations. The results showed that TGP selectively enhanced the number of the eosinophilic bacterium Lactobacillus johnsonii, which was reduced in HFD mice. Of note, the oral administration of L. johnsonii formulations to HFD mice alleviated NAFLD, and this was related to regulating lipid metabolism and the accumulation of lipids in the liver. Therefore, the current study uncovered a potential pathway for developing NAFLD treatment strategies based on the interaction between TGP and the gut microbiota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in recent years, but the pathogenesis is not fully understood. Therefore, it is important to establish an effective animal model for studying NAFLD., Methods: Adult zebrafish were fed a normal diet or a high-fat diet combined with egg yolk powder for 30 days. Body mass index (BMI) was measured to determine overall obesity. Serum lipids were measured using triglyceride (TG) and total cholesterol (TC) kits. Liver lipid deposition was detected by Oil Red O staining. Liver injury was assessed by measuring glutathione aminotransferase (AST) and glutamic acid aminotransferase (ALT) levels. Reactive oxygen species (ROS) and malondialdehyde (MDA) were used to evaluate oxidative damage. The level of inflammation was assessed by qRT-PCR for pro-inflammatory factors. H&E staining was used for pathological histology. Caspase-3 immunofluorescence measured apoptosis. Physiological disruption was assessed via RNA-seq analysis of genes at the transcriptional level and validated by qRT-PCR., Results: The high-fat diet led to significant obesity in zebrafish, with elevated BMI, hepatic TC, and TG. Severe lipid deposition in the liver was observed by ORO and H&E staining, accompanied by massive steatosis and ballooning. Serum AST and ALT levels were elevated, and significant liver damage was observed. The antioxidant system in the body was severely imbalanced. Hepatocytes showed massive apoptosis. RNA-seq results indicated that several physiological processes, including endoplasmic reticulum stress, and glucolipid metabolism, were disrupted., Conclusion: Additional feeding of egg yolk powder to adult zebrafish for 30 consecutive days can mimic the pathology of human nonalcoholic fatty liver disease., (© 2023 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Background: Obesity is a significant risk factor for the progression of non-alcoholic fatty liver disease (NAFLD). However, a convenient and efficacious non-invasive test for monitoring NAFLD progression in patients with obesity is currently lacking. This study aims to investigate the associations between CT-based body composition and the progression of biopsy-proven NAFLD in patients with obesity., Methods: Liver biopsy was conducted in patients with obesity, and the progression of NAFLD was evaluated by the NAFLD activity score (NAS). Body composition was assessed through abdominal computed tomography (CT) scans., Results: A total of 602 patients with an average age of 31.65 (±9.33) years old were included, comprising 217 male patients and 385 female patients. The wall skeletal muscle index (SMI), total SMI, and visceral fat index (VFI) were positively correlated with NAS in both male and female patients. Multivariate regression analysis demonstrated significant associations between high liver steatosis and wall SMI (HR: 1.60, 95% CI: 1.12 to 2.30), total SMI (HR: 1.50, 95% CI: 1.02 to 2.08), VSI (HR: 2.16, 95% CI: 1.48 to 3.14), visceral fat to muscle ratio (HR: 1.51, 95% CI: 1.05 to 2.18), and visceral to subcutaneous fat ratio (HR: 1.51, 95% CI: 1.07 to 2.12). Non-alcoholic steatohepatitis (NASH) was significantly associated with wall SMI (HR: 1.52, 95% CI: 1.06 to 2.19) and VSI (HR: 1.50, 95% CI: 1.03 to 2.17). Liver fibrosis ≥ F2 was significantly associated with psoas muscle index (HR: 0.64, 95% CI: 0.44 to 0.93) and psoas skeletal muscle density (HR: 0.61, 95% CI: 0.41 to 0.89)., Conclusions: Our study suggested that certain CT-based body composition indicators, notably high VFI, were significantly associated with the progression of NAFLD in patients with obesity. Great attentions and timely managements should be given to these patients with body composition characteristics associated with the risk of NAFLD progression., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder worldwide, with an increasing incidence in recent years. While previous studies have suggested an association between the air pollutant PM2.5 and NAFLD, there is still considerable debate regarding the existence of a clear causal relationship between air pollution and NAFLD. This study aims to employ Mendelian randomization methods to evaluate the causal relationship between major air pollutants and NAFLD., Method: We conducted Mendelian randomization analyses on a large-scale publicly available genome-wide association study (GWAS) dataset of European populations to dissect the association between air pollutants, NAFLD, and liver function indicators. We used five different analysis methods, including Inverse-variance weighted (IVW), Weighted median, MR-Egger, Simple mode, and Weighted mode, to analyze the data. We also tested for pleiotropy, heterogeneity, and sensitivity of the results., Results: This study utilized four common exposures related to air pollution and four outcomes related to NAFLD. The results regarding the association between air pollutants and NAFLD (PM2.5: P =0.808, 95% CI=0.37-3.56; PM10: P =0.238, 95% CI=0.33-1.31; nitrogen dioxide: P =0.629, 95% CI=0.40-4.61; nitrogen oxides: P =0.123, 95% CI=0.13-1.28) indicated no statistically significant correlation between them. However, notably, there was a causal relationship between PM10 and serum albumin (ALB) levels ( P =0.019, 95% CI=1.02-1.27)., Conclusion: This MR study found no evidence of a causal relationship between air pollution and NAFLD in European populations. However, a statistically significant association was observed between PM10 and ALB levels, suggesting that the air pollutant PM10 may impact the liver's ability to synthesize proteins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Pan, Pan, Zheng, Fan, Zhen, Pi, Liang, Shen, Li, Yang and Zhang.)

Helicobacter pylori infection has been investigated as a potential risk factor for non-alcoholic fatty liver disease (NAFLD). Some studies suggest a possible link between the two conditions. The purpose of this study is to study the relationship between H. pylori infection and NAFLD in pediatrics and its relation to NAFLD grades. A case-control study to identify predictors of NAFLD and a comparative cross-sectional approach to determine factors affecting NAFLD grades were adopted. One hundred NAFLD children (ultrasound-based) and a control group of 100 non-NAFLD children were recruited. Both groups were evaluated by detecting H. pylori stool antigen. Immunoglobulin G antibodies to Cag A (cytotoxin-associated gene A), Vac A (vacuolating cytotoxin A), Gro EL (chaperonin Gro EL), HCPC (Helicobacter cysteine-rich protein C), and Ure A (Urease subunit A) were assessed in the serum of those with positive stool antigen. H. pylori infection was significantly higher in NAFLD children compared to the control group (64% versus 25%, p-value < .001). (NAFLD children showed higher Cag A and Vac A positivity (34, 10%) versus (2%, 0%) in the control group, respectively, p-value < .001). The regression model showed that H. pylori positivity (OR (odds ratio) = 5.021, 95% CI (confidence interval): 1.105-22.815), homeostatic model assessment of insulin resistance (Homa IR) (OR = 18.840, 95% CI: 3.998-88.789), waist percentile (OR = 1.184, 95% CI: 1.044-1.344), and triglycerides (OR = 1.029, 95% CI: 1.012-1.047) were predictors for NAFLD. Cag A positivity (OR = 2.740, 95% CI: 1.013-7.411) was associated with higher NAFLD grade (grade 2 fatty liver)., Conclusions: H. pylori infection could increase the risk of NAFLD in children. Triglycerides, waist circumference, and Homa IR are significant independent predictors of NAFLD., What Is Known: • NAFLD has become one of the most common liver diseases among children because of the increased prevalence of pediatric obesity. • Dyslipidemia and insulin resistance play a central role in NAFLD pathogenesis. • NAFLD could be explained by the multiple-hit hypothesis. The gut microbiota is an important factor in this hypothesis (gut liver axis)., What Is New: • Helicobacter pylori infection could increase the risk of NAFLD in children. • H. pylori Cytotoxin-associated gene A (Cag A) positivity is associated with higher NAFLD grade., Competing Interests: Declarations. Ethics approval: The research was approved by the Ethics Committee of the Faculty of Medicine – Alexandria University (17/11/2022) in accordance with ICH GCP (International Council for Harmonisation Good Clinical Practice) guidelines with registry number 0201736. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

To explore the therapeutic effects along with the molecular mechanisms of epigallocatechin gallate (EGCG) in non-alcoholic fatty liver disease (NAFLD) treatment using network pharmacology as well as animal experiments. Firstly, the Traditional Chinese Medicine (TCM) Systems Pharmacology Database was searched to identify the potential targets of EGCG. The DisGeNET Database was used to screen the potential targets of NAFLD. The GeneCards Database was searched to identify related genes involved in pyroptosis. Subsequently, the intersecting genes of EGCG targeting pyroptosis to regulate NAFLD were obtained using a Venn diagram. Simultaneously, the aforementioned intersecting genes were used to construct a drug-disease target protein-protein interaction (PPI) network. The DAVID database was adopted for Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The main pathway-target network was determined. Next, the potential mechanism of EGCG targeting pyroptosis to regulate NAFLD was investigated and validated through in vivo experiments. 626 potential targets of EGCG, 447 target genes of NAFLD, and 568 potential targets of pyroptosis were identified. The number of common targets between EGCG, NAFLD, and pyroptosis was 266. GO biological process items and 92 KEGG pathways were determined based on the analysis results. Animal experiments demonstrated that EGCG could ameliorate body weight, glucolipid metabolism, steatosis, and liver injury, enhance insulin sensitivity, and improve glucose tolerance in NAFLD mice through the classical pathway of pyroptosis. EGCG could effectively treat NAFLD through multiple targets and pathways. It was concluded that EGCG ameliorates hepatocyte steatosis, pyroptosis, dyslipidemia, and inflammation in NAFLD mice fed a high-fat diet (HFD), and the protective mechanism could be associated with the NLRP3-Caspase-1-GSDMD classical pyroptosis pathway., Competing Interests: Declaration of competing interest The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Investigating the causal relationship between inflammatory cytokines and Non-alcoholic fatty liver disease(NAFLD) and identifying and quantifying the role of serum ferritin as a potential mediator., Methods: Genetic summary statistics were derived from open genome-wide association study (GWAS) databases. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the relationship between inflammatory cytokines (8,293 individuals) and NAFLD (8,434 cases, 770,180 controls). Furthermore, we used two-step MR to quantitate the proportion of the effect of serum ferritin-mediated inflammatory cytokines on NAFLD. In this study, we primarily utilized inverse-variance-weighted Mendelian randomization (MR-IVW) and reverse MR analysis methods, while other methods were also performed for sensitivity analysis, false discovery rate (FDR) <0.0012 as statistical significance in MR analyses., Results: Our results indicated that high levels of Eotaxin, regulated upon activation normal T cell expressed and presumably secreted(RANTES), Interleukin-2(IL-2), macrophage migration inhibitory factor(MIF), tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) and Stem cell factor(SCF) were associated with increased risks of NAFLD, while high Cutaneous T cell-attracting chemokine(CTACK) and Interleukin-16(IL-16) levels that reduced the risk of NAFLD.The proportion of genetically predicted NAFLD mediated by ferritin was 2.1%(95% CI = 1.39%-5.61%)., Conclusion: In conclusion, our study identified a causal relationship between inflammatory cytokines and NAFLD, with a small proportion of the effect mediated by ferritin, but a majority of the effect of inflammatory cytokines on NAFLD remains unclear. Further research is needed on additional risk factors as potential mediators., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Jin, Wang and Ge.)

Non-alcoholic fatty liver disease (NAFLD) presents a pervasive global pandemic, affecting approximately 25 % of the world's population. This grave health issue not only demands urgent attention but also stands as a significant economic concern on a global scale. The genesis of NAFLD can be primarily attributed to unhealthy dietary habits and a sedentary lifestyle, albeit certain genetic factors have also been recorded to contribute to its occurrence. NAFLD is characterized by fat accumulation in more than 5 % of hepatocytes according to histological analysis, or >5.6 % of lipid volume fraction in total liver weight in patients. The pathophysiology of NAFLD/non-alcoholic steatohepatitis (NASH) is multifactorial and the mechanisms underlying the progression to advanced forms remain unclear, thereby representing a challenge to disease therapy. Despite the substantial efforts from the scientific community and the large number of pre-clinical and clinical trials performed so far, only one drug was approved by the Food and Drug Administration (FDA) to treat NAFLD/NASH specifically. This review provides an overview of available information concerning emerging molecular targets and drug candidates tested in clinical studies for the treatment of NAFLD/NASH. Improving our understanding of NAFLD pathophysiology and pharmacotherapy is crucial not only to explore new molecular targets, but also to potentiate drug discovery programs to develop new therapeutic strategies. This knowledge endeavours scientific efforts to reduce the time for achieving a specific and effective drug for NAFLD or NASH management and improve patients' quality of life., Competing Interests: Declaration of competing interest All listed authors s have contributed to the manuscript substantially and have agreed to the final submitted version., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To explore the interaction between pediatric sleep-disordered breathing（SDB）, the intestinal microbiota, and pediatric non-alcoholic fatty liver disease（NAFLD）. Methods: A total of 63 non-obese children（47 children with SDB in the experimental group and 16 without SDB in the control group） were enrolled in this study. The liver function and degree of SDB were assessed in both groups. High-throughput 16S rRNA sequencing was conducted to detect the composition and functional variations of the intestinal microbiota in the two groups of children. Results: Compared with children in the experimental group, serum ALT and AST levels were higher in the control group. and the relative proteobacteria abundance of intestinal flora increased, and the relative abundance of Bacteroidetes decreased significantly. Function including membrane transport, carbohydrate metabolism and lipid metabolism, were enriched in the intestinal microbiota of children with SDB. Conclusion: The composition and functional annotation of the pediatric liver functional status and gut microbiota were significantly different between the two groups of children with and without SDB. Changes in SDB-associated intestinal bacterial abundance may be related to the pathogenesis of pediatric NAFLD., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. The increasingly sedentary lifestyle in recent years may have accelerated the development of NAFLD, independent of the level of physical activity., Objective: The purpose of this cross-sectional study was to determine the association between leisure-time physical activity (LTPA) and time spent sitting (TSS) and the likelihood of developing NAFLD in a sample of men and women aged 18-64 years, from southern Italy., Design: The study is based on two cohort studies, a randomized clinical trial and an observational cost-benefit study., Participants: A total of 1269 participants (51.5% women) drawn from 3992 eligible subjects were enrolled in this study., Exposures: Leisure-time physical activity (LTPA) and time spent sitting (TSS) were assessed using the Italian long form of the International Physical Activity Questionnaire (IPAQ-LF), designed for administration to adults aged 18 to 65 years., Main Measures: The association of exposures with the probability of belonging to a certain NAFLD degree of severity., Key Results: The probability of having mild, moderate, and severe NAFLD tends to decrease with increasing LTPA and decreasing TSS levels. We selected a combination of participants aged 50 years and older stratified by gender. Men had a statistically significant difference in the probability of developing moderate NAFLD if they spent 70 h per week sitting and had low LTPA, while among women there was a statistically significant difference in the probability of developing mild or moderate NAFLD if they had moderate LPTA and spent 35-70 h/week sitting., Conclusions: The study thus showed that the amount of LTPA and the amount of TSS are associated with development and progression of NAFLD, but this relationship is not a linear one-especially in women aged ≥ 50 years old., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Zexie-Baizhu Decoction (AA), a Chinese Classical Formula composed of Alisma orientalis (Sam.) Juzep. and Aractylodes Macrocephala Koidz in the specific ratio of 5:2, has a long history of use in treating metabolic disorders. Recent studies have demonstrated AA's ameliorative effects on non-alcoholic fatty liver disease (NAFLD); however, the mechanism underlying its action on the gut and adipose tissue, key regulators of metabolism, have not been fully explored., Aim of the Study: This study aimed to investigate the mechanisms by which AA regulates the homeostasis of gut and adipose tissue in NAFLD., Materials and Methods: AA (1500 mg/kg/day) or vehicle was administrated to the high-fat diet-induced and normal chow-fed mice (C57BL/6J). Plasma, the liver, gut microbiota, bile acids, and short-chain fatty acids in the gut, were systematically investigated. RNA sequencing analysis, reverse transcription quantitative real-time PCR, and Western Blotting were performed on the epididymal white adipose tissues (eWAT) to explore AA's influence on NAFLD. Lipidomics of the liver and eWAT were analyzed by liquid chromatography-mass spectrometry and desorption electrospray ionization mass spectrometry imaging., Results: Our study demonstrated that AA administration effectively alleviated liver injury induced by NAFLD, as evidenced by reduced hepatic fat accumulation and inflammation. Mechanistically, AA modulated the composition of the gut microbiota, promoting the growth of beneficial bacteria such as Akkermansia muciniphila and restoring the balance between Firmicutes and Bacteroidetes. Furthermore, AA regulated the levels of bile acids and short-chain fatty acids in the intestine, plasma, and liver. Correspondingly in the eWAT, AA administration activated bile acid receptor (Gpbar1) and short-chain fatty acid receptor (Ffar2), facilitating lipid breakdown and attenuating triglyceride accumulation. Transcriptome analysis revealed that AA influenced gene expression related to fatty acid metabolism, thermogenesis, insulin resistance, AMPK signaling, and the tricarboxylic acid (TCA) cycle, thereby improving NAFLD at the transcriptional level. Additionally, AA treatment significantly altered the lipid composition in the liver, reducing levels of diacylglycerols, triacylglycerols, phosphatidylserines, and cholesterol esters, while increasing levels of phosphatidic acids, phosphatidylethanolamines, and sphingomyelins., Conclusion: Our study builds a connection between the gut and adipose tissue to understand the mechanism of AA on alleviating NAFLD, providing new insights into the development of targeted therapies for this condition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The present study explored the association between biological aging (BA), healthy eating index-2015 (HEI-2015) and non-alcoholic fatty liver disease (NAFLD) in the general population of the United States., Methods: We used data from the NHANES database between 2017-2018 years to conduct the study. Weighted multivariable logistic regression analysis, restricted cubic spline (RCS), and subgroup analysis were performed to analyze the association of BA and HEI-2015 with prevalence of NAFLD and the mediation effect of HEI-2015 was also discussed. Additionally, generalized additive model was conducted to investigate the association of BA and HEI-2015 with ZJU index, BARD score, and NAFLD fibrosis score., Results: There was a total of 2,421 individuals. RCS shown that BA was positively correlated with prevalence of NAFLD, while HEI-2015 was negative correlated with NAFLD risk. After adjusting for interfering factors, compared with the lowest quartiles of BA and HEI-2015, the odds ratios with 95% confidence intervals for NAFLD across the quartiles were (1.24 (0.84, 1.84), 2.07 (1.15, 3.73) and 2.49 (1.16, 5.38)) and (0.89 (0.66, 1.18), 0.87 (0.65, 1.16) and 0.64 (0.46, 0.87)), respectively. The BA was linear positive with ZJU index, BARD score and NAFLD fibrosis score. However, the linear negative correlation existed between HEI-2015 and ZJU index, BARD score and NAFLD fibrosis score. Mediation analysis showed that the positive correlation between BA and NAFLD could be mediated and weakened by HEI-2015., Conclusions: The prevalence of NAFLD gradually increases with BA, but this positive association can be weakened by the healthy diet., Competing Interests: Declarations. Ethics approval and consent to participate: All NHANES participants provided written informed consent and the National Center for Health Statistics obtained institutional review board approval prior to data collection. Because NHANES data are de-identified and publicly available, the analysis presented here was exempt from IRB review. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Rapamycin (Rapa) is an inhibitor of mTOR complex, and its therapeutic effect on liver function was examined in non-alcoholic fatty liver disease (NAFLD) rats here. And the possible mechanism of Rapa in NAFLD was preliminarily elucidated based on the non-targeted metabolomics analysis. Adult male SD rats were fed with a high-fat and high-cholesterol diet (HFD) to establish NAFLD model. For Rapa group, 0.8 mg/(kg.d) Rapa was given to the HFD rats. Ultra-performance liquid chromatography and Q-Tof-mass spectrometry (UPLC and Q-TOF/MS) analysis were applied for the identification of metabolites in the serum of rats, which were annotated using Kyoto Encyclopedia of Genes and Genomes (KEGG). NAFLD rats presented with disturbed liver function, lipid metabolism and oxidative stress, but Rapa exerted a mitigating influence on the disorders. The metabolite profile data identified 579 metabolites that varied remarkably between the Rapa and HFD groups, with the main classes of amino acids and peptides, benzene, lipids and fatty acids. The differential metabolites were mainly involved in biosynthesis of cofactors, bile secretion, and glycerophospholipid metabolism were mainly enriched. In conclusion, Rapa has a potential protective effect against HFD-induced NAFLD, its hepatoprotective effect may achieved through mediating bile secretion and glycerophospholipid metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Build-up of free cholesterol (FC) substantially contributes to the development and severity of non-alcoholic fatty liver disease (NAFLD). Here, we investigate the specific mechanism by which FC induces liver injury in NAFLD and propose a novel therapeutic approach using dihydrotanshinone I (DhT). Rather than cholesterol ester (CE), we observed elevated levels of total cholesterol, FC, and alanine transaminase (ALT) in NAFLD patients and high-cholesterol diet-induced NAFLD mice compared to those in healthy controls. The FC level demonstrated a positive correlation with the ALT level in both patients and mice. Mechanistic studies revealed that FC elevated reactive oxygen species level, impaired the function of lysosomes, and disrupted lipophagy process, consequently inducing cell apoptosis. We then found that DhT protected mice on an HCD diet, independent of gut microbiota. DhT functioned as a potent ligand for peroxisome proliferator-activated receptor α (PPARα), stimulating its transcriptional function and enhancing catalase expression to lower reactive oxygen species (ROS) level. Notably, the protective effect of DhT was nullified in mice with hepatic PPARα knockdown. Thus, these findings are the first to report the detrimental role of FC in NAFLD, which could lead to the development of new treatment strategies for NAFLD by leveraging the therapeutic potential of DhT and PPARα pathway., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background/introduction: To evaluate the performance of pre-trained deep learning schemes (DLS) in hepatic steatosis (HS) grading of Non-Alcoholic Fatty Liver Disease (NAFLD) patients, using as input B-mode US images containing right kidney (RK) cortex and liver parenchyma (LP) areas indicated by an expert radiologist., Methods: A total of 112 consecutively enrolled, biopsy-validated NAFLD patients underwent a regular abdominal B-mode US examination. For each patient, a radiologist obtained a B-mode US image containing RK cortex and LP and marked a point between the RK and LP, around which a window was automatically cropped. The cropped image dataset was augmented using up-sampling, and the augmented and non-augmented datasets were sorted by HS grade. Each dataset was split into training (70%) and testing (30%), and fed separately as input to InceptionV3, MobileNetV2, ResNet50, DenseNet201, and NASNetMobile pre-trained DLS. A receiver operating characteristic (ROC) analysis of hepatorenal index (HRI) measurements by the radiologist from the same cropped images was used for comparison with the performance of the DLS., Results: With the test data, the DLS reached 89.15 %-93.75 % accuracy when comparing HS grades S0-S1 vs. S2-S3 and 79.69 %-91.21 % accuracy for S0 vs. S1 vs. S2 vs. S3 with augmentation, and 80.45-82.73 % accuracy when comparing S0-S1 vs. S2-S3 and 59.54 %-63.64 % accuracy for S0 vs. S1 vs. S2 vs. S3 without augmentation. The performance of radiologists' HRI measurement after ROC analysis was 82 %, 91.56 %, and 96.19 % for thresholds of S ≥ S1, S ≥ S2, and S = S3, respectively., Conclusion: All networks achieved high performance in HS assessment. DenseNet201 with the use of augmented data seems to be the most efficient supplementary tool for NAFLD diagnosis and grading., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study is to utilize two-sample Mendelian randomization (MR) to investigate the potential causal relationship among psoriasis, iridocyclitis, and non-alcoholic fatty liver disease (NAFLD), and to explore any potential mediation effects. Methods: Pooled data were derived from the public genome-wide association study (GWAS) in NAFLD (finn-b-NAFLD), iridocyclitis (finn-b-H7&#95;IRIDOCYCLITIS) and psoriasis (finn-b-L12&#95;PSORI&#95;VULG). Univariable MR (UVMR) analysis was implemented to explore the causal relationship among psoriasis, iridocyclitis, and NAFLD, and inverse variance weighting (IVW) was used as the primary analytical method. Additionally, Cochran's Q and MR-Egger tests were utilized to evaluate the heterogeneity and horizontal pleiotropy, respectively. Simultaneously, the reliability of MR results was evaluated by leave-one-out (LOO) method. Finally, multivariable MR (MVMR) analysis and mediation analysis were performed to further reveal the mechanism of mediation effect among the three diseases. Results: With regard to the results of IVW method, both iridocyclitis ( P =0.0185, OR=1.0757) and psoriasis ( P =0.0115, OR=1.1246) had significant causal relationships with the occurrence of NAFLD, and both were risk factors for NAFLD. Besides, it was observed that there was significant causal effect of iridocyclitis ( P = 0.0181, OR=1.1729) on psoriasis and iridocyclitis was a risk factor. Additionally, there was a lack of heterogeneity ( P >0.05) among the selected SNPs when MR analysis was conducted with NAFLD as the outcome. Horizontal pleiotropy was not detected by the MR-Egger test. The LOO analysis demonstrated that the instrumental variables were appropriately chosen, suggesting the reliability of the MR results. Ultimately, MVMR and mediation analysis revealed iridocyclitis affected the development of NAFLD, 20.81% of which was caused by the pathway of iridocyclitis induced psoriasis leading to NAFLD. Conclusion: This study highlighted that iridocyclitis was significantly associated with an increased risk of NAFLD and that psoriasis was involved in the mechanism by which iridocyclitis triggered NAFLD, which might offer potential preventive strategies for NAFLD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver alterations worldwide, being gut microbiota dysbiosis one of the contributing factors to its development. The aim of this research is to compare the potential effects of a viable probiotic (Lactobacillus rhamnosus GG) with those exerted by its heat-inactivated paraprobiotic counterpart in a dietary rodent model of NAFLD. The probiotic administration effectively prevented the hepatic lipid accumulation induced by a high-fat high-fructose diet feeding, as demonstrated by chemical (lower TG content) and histological (lower steatosis grade and lobular inflammation) analyses. This effect was mainly mediated by the downregulation of lipid uptake (FATP2 protein expression) and upregulating liver TG release to bloodstream (MTTP activity) in rats receiving the probiotic. By contrast, the effect of the paraprobiotic preventing diet-induced liver lipid accumulation was milder, and mainly derived from the downregulation of hepatic de novo lipogenesis (SREBP-1c protein expression and FAS activity) and TG assembly (DGAT2 and AQP9 protein expression). The obtained results demonstrate that under these experimental conditions, the effects induced by the administration of viable L. rhamnosus GG preventing liver lipid accumulation in rats fed a diet rich in saturated fat and fructose differ from those induced by its heat-inactivated paraprobiotic counterpart., (© 2024 The Author(s). BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Background and Objective: A systematic review and meta-analysis were used to investigate the relationship between air pollution exposure and the prevalence of non-alcoholic fatty liver disease (NAFLD) and its related cirrhosis. Through this study, we hope to clarify the potential public health risks of air pollution as an environmental exposure factor., Methods: Through a comprehensive and systematic search of the EMBASE, PubMed, Web of Science, and Cochrane library databases, studies published up to March 30, 2024, that met the eligibility criteria were identified. The meta-analysis aimed to determine the association between air pollution exposure and NAFLD risk. Subgroup analyses were conducted based on regional economic development after adjusting for confounding factors. The combined odds ratio (OR) was calculated, publication bias was assessed using funnel plots, and consideration was given to heterogeneity among study-specific relative risks., Results: This review included 14 observational studies (including 7 cohort studies and 7 cross-sectional studies) involving 43,475,41 participants. The pooled analysis showed that PM 2.5 , NO x , PM 10 , PM 2.5-10 , passive smoking, PM 1 , and air pollution from solid fuels were positively associated with the incidence and prevalence of NAFLD and its related cirrhosis. The risk ratios for PM 2.5 , NO x , PM 10 , PM 2.5-10 , passive smoking, and air pollution from solid fuels for NAFLD and its related cirrhosis were 1.33 (95 % CI: 1.25, 1.42), 1.19 (95 % CI: 1.14, 1.23), 1.27 (95 % CI: 1.05, 1.55), 1.05 (95 % CI: 1.00, 1.11), 1.53 (95 % CI: 1.12, 2.09), 1.50 (95 % CI: 0.86, 2.63), and 1.18 (95 % CI: 0.85, 1.63), respectively. In contrast, the risk ratio for O 3 was 0.75 (95 % CI: 0.69, 0.83), suggesting that O 3 may lower the incidence and prevalence of NAFLD and its related cirrhosis. We also conducted subgroup analyses based on the level of national development to examine the impact of PM 2.5 on NAFLD and its related cirrhosis. The results showed that the risk of NAFLD and its related cirrhosis associated with PM 2.5 in developing countries was 1.41 (95 % CI: 1.29, 1.53), which was higher than 1.20 (95 % CI: 1.12, 1.29) in developed countries., Conclusion: The study findings show that PM 2.5 , NO x , PM 10 , PM 2.5-10 , passive smoking, PM 1 , and air pollution from solid fuels can increase an individual's risk of developing NAFLD and its related cirrhosis; while O 3 can reduce the risk. In developing countries, the risk level of NAFLD and its related cirrhosis due to PM 2.5 is higher than that in developed countries., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xueping Li reports financial support was provided by The National Natural Science Foundation of China. Xueping Li reports financial support was provided by The Natural Science Foundation of Science and Technology Department of Sichuan Province. Xueping Li reports financial support was provided by Xinglin Scholar Research Promotion Project of Chengdu University of Traditional Chinese Medicine. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) has been recognized as an independent risk factor for atherosclerotic cardiovascular disease. Recently, there has been a shift towards diagnosing metabolic dysfunction-associated fatty liver disease (MAFLD), offering simplified criteria and improved risk assessment. However, the association between MAFLD and carotid atherosclerosis remains poorly understood., Methods and Results: The study analyzed the association of concurrent carotid atherosclerosis between NAFLD and MAFLD patients with a retrospective cohort design. The study enrolled participants who underwent abdominal and carotid artery ultrasounds from a medical center in Taiwan. NAFLD and MAFLD were diagnosed based on imaging and specific criteria. Associations between NAFLD, MAFLD, and carotid atherosclerosis were analyzed using logistic regression. Among 11,194 participants, 57.1 % were diagnosed with fatty liver disease, among which the NAFLD-MAFLD group comprised 4689 individuals, with 900 in the NAFLD-only group and 669 in the MAFLD-only group. Significant demographic and clinical differences were observed between groups. Logistic regression showed that the MAFLD-NAFLD group and MAFLD-only group had significantly higher odds of concomitant carotid atherosclerosis. Among MAFLD patients, 65.5 % had concurrent carotid arteriosclerosis with an odds ratio of 2.35 compared to non-MAFLD patients. The odds ratios for variables in MAFLD patients, such as diabetes mellitus, Fibrosis-4(FIB-4), number of FIB-4 > 1.3, and number of NAFLD fibrosis score > -1.455 were all greater than 2., Conclusions: MAFLD is associated with a higher prevalence of carotid atherosclerosis, compared to NAFLD. This suggests that MAFLD may serve as a significant risk factor for cardiovascular complications., Competing Interests: Declaration of competing interest The authors declare no competing interests related to the present study., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Adipose tissue-derived adipokines facilitate inter-organ communication between adipose tissue and other organs. Omentin-1, an adipokine, has been implicated in the regulation of glucose and insulin metabolism. However, limited knowledge exists regarding the regulatory impact of endogenous omentin-1 on hepatic steatosis. C57BL/6J mice were fed with high-fat diet (HFD) for 8 weeks to induce nonalcoholic fatty liver disease (NAFLD), while HepG2 cells were exposed to a 0.1 mM free fatty acid (FFA) mixture for 24 h to induce hepatic steatosis. Both the mice and cells were treated with omentin-1, and the therapeutic effects as well as the underlying molecular mechanisms were investigated. Our data demonstrate that omentin-1 attenuates weight and fat mass gain, preserves glucose homeostasis, normalizes the expression of lipogenesis-related proteins, and alleviates hepatic lipid accumulation in HFD fed mice. Furthermore, omentin-1 normalized AMPKα/mTOR signaling and preserves autophagy in these mice. In vitro, omentin-1 also preserves autophagy and attenuates lipid accumulation by normalizing AMPKα/mTOR signaling in a cell model of FFA treated HepG2 cells. However, inhibition of AMPK with Compound C or AMPKα whole-body knockout reverses the above beneficial effects of omentin-1. The present study demonstrates that omentin-1 exerts a preventive effect on non-alcoholic fatty liver disease (NAFLD) by preserving autophagy through normalizing the AMPKα/mTOR pathway, thereby suggesting its potential as a promising therapeutic agent against NAFLD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Non-alcoholic fatty liver disease (NAFLD) is estimated to affect a third of Australian adults, and its prevalence is predicted to rise, increasing the burden on the healthcare system. The LOCal Assessment and Triage Evaluation of Non-Alcoholic Fatty Liver Disease (LOCATE-NAFLD) trialled a community-based fibrosis assessment service using FibroScan to reduce the time to diagnosis of high-risk NAFLD and improve patient outcomes., Methods: We conducted a 1:1 parallel randomised trial to compare two alternative models of care for NAFLD diagnosis and assessment. Participants had suspected NAFLD and were referred to a hepatology clinic in one of three major hospitals in South-East Queensland. Eligible consenting participants were randomised to receive usual care or the intervention (LOCATE). Participants in the intervention arm received a FibroScan outside of the hospital setting, with results provided to their primary care provider and the referring hepatologist. All participants were followed up 12 months after randomisation to measure their clinical and patient-reported outcomes., Results: 97 participants were recruited from October 2020 to December 2022. Of the 50 participants randomised to the intervention arm, one failed to attend their appointment, and of the 48 (98%) who had a FibroScan 13 (27%) had a liver stiffness measurement of 8.0 kPa or greater. The HR for the time to diagnosis of high risk was 1.28 (95% CI 0.59 to 2.79), indicating a faster average time to diagnosis with the intervention, but failing to conclusively demonstrate a faster time. The intervention did greatly reduce the time to FibroScan by almost 1 year (median difference 0.92 years, 95% CI 0.56 to 1.45). Other clinical outcomes showed minimal changes., Conclusion: The LOCATE model shows potential for impact, particularly in reducing waiting times for patients at high risk of developing severe liver disease due to NAFLD. A larger sample and longer follow-ups are needed to measure additional clinical outcomes., Trial Registration Number: ACTRN12620000158965., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Air pollution has been linked with non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms characterized by perturbations in the circulating proteome profile are largely unknown. Therefore, we included 51,357 participants from the UK Biobank with 2941 plasma proteins measured in blood samples collected between 2006 and 2010, measurements of annual fine particular matter <2.5 μm in diameter (PM 2.5 ) and nitrogen dioxide (NO 2 ), and follow-up data on NAFLD (743 incident cases occurred over a median follow-up of 13.6 years). Multiple linear regression was used to identify proteins associated with PM 2.5 and NO 2 . Cox proportional hazards models were applied to assess associations of PM 2.5 and NO 2 and identified proteins with incident NAFLD. Mediation analyses were conducted to explore the mediation role of proteins in the associations between air pollution and incident NAFLD. After adjusting for selected covariates, PM 2.5 (hazard ratio [HR] = 2.57, 95%CI:1.27, 5.21, per ln increase) and NO 2 (HR = 1.43, 95%CI: 1.10, 1.84, per ln increase) were positively associated with incident NAFLD. We identified 138 proteins associated with PM 2.5 (92 positively, 46 inversely, FDR <0.05) and 143 with NO 2 (100 positively, 43 inversely). Of the proteins that were significantly associated with both PM 2.5 and NO 2 , 93 (79 positively, 14 inversely) and 79 (69 positively, 10 inversely) were significantly associated with incident NAFLD. Furthermore, 84 PM 2.5 -associated proteins and 66 NO 2 -associated proteins significantly mediated the corresponding association between air pollutants and incident NAFLD, with the proportion of mediation effects ranging from 3.2 % to 27.3 % for PM 2.5 and 2.6 % to 20.8 % for NO 2 , respectively. Of note, the majority of significant mediating proteins were enriched in pathways of cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor. Our findings suggested that long-term exposure to PM 2.5 and NO 2 was associated with an increased risk of NAFLD partially by perturbating circulating proteins involved in pathways of inflammation and immunity responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Atherosclerosis (AS) and Non-alcoholic fatty liver disease (NAFLD) are chronic metabolic disorders with high prevalence and significant health impacts. Both conditions share common pathophysiological pathways including abnormal lipid metabolism and inflammation. Berberine (BBR), an isoquinoline alkaloid, is known for its beneficial effects on various metabolic and cardiovascular disorders. This study investigates BBR's impact on AS and NAFLD through bioinformatics analysis and experimental models. This study utilized various bioinformatics methods, including transcriptome analysis, weighted gene co-expression network analysis (WGCNA), machine learning, and molecular docking, to identify key genes and pathways involved in AS and NAFLD. Subsequently an animal model of AS combined with NAFLD was established using ApoE-/- mice fed a high-fat diet. The efficacy and mechanism of action of BBR were verified using methods such as hematoxylin and eosin (HE) staining, Oil Red O staining, and real-time quantitative PCR (RTqPCR). Through transcriptome analysis, WGCNA, and machine learning, this study identified 48 key genes involved in both AS and NAFLD. Function analysis revealed that the implicated genes were significantly involved in pathways like cytokine-cytokine receptor interaction, chemokine signaling, and IL-17 signaling pathway, suggesting their role in inflammation and immune responses. Single cell validation identified six key genes: dual specificity phosphatase 6 (DUSP6), chemokine ligand 3 (CCL3), complement component 5a receptor 1 (C5AR1), formyl peptide receptor 1 (FPR1), myeloid nuclear differentiation antigen (MNDA), and proviral integration site of murine 2(PIM2). Finally, molecular docking and animal experiments showed that BBR significantly reduced lipid deposits and inflammatory markers in liver and aortic tissues. In conclusion, BBR can improve AS combined with NAFLD by regulating genes like MNDA, PIM2, DUSP6, CCL3, C5AR1, and FPR1, with the mechanism related to inflammation control. The findings suggest potential clinical benefits of BBR in reducing the progression of both AS and NAFLD, warranting further investigation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Data on risk of developing chronic kidney disease (CKD) between non-obese and obese non-alcoholic fatty liver disease (NAFLD) patients are limited. We aimed to reveal the risk difference of incident CKD between non-obese and obese NAFLD patients., Methods: We searched PubMed, Embase, and Web of Science databases for studies which reported the incidence of CKD in non-obese and obese NAFLD from inception to 10 March 2024. The primary and secondary outcomes were pooled. Subgroup analysis was used to examine the heterogeneity., Results: A total of 15 studies were incorporated. The incidence of CKD in non-obese and obese NAFLD were 1,450/38,720 (3.74%) and 3,067/84,154 (3.64%), respectively. Non-obese NAFLD patients had a comparable risk of CKD as obese NAFLD (odds ratio [OR] 0.92, 95% confidence interval [95% CI] [0.72-1.19], I 2 = 88%). No differences in estimated glomerular filtration rate and serum creatinine between non-obese and obese NAFLD were found. The mean differences (MD) and 95% CI were 0.01 [-0.02 to 0.04] and 0.50 [-0.90 to 1.90], respectively. In subgroup analyses, non-obese NAFLD had higher eGFR when diagnosed with ultrasound (MD 1.45, 95% CI [0.11-2.79], I 2 = 21%). Non-obese NAFLD had higher creatinine in non-Asian (MD 0.06, 95% CI [0.01-0.11], I 2 = 55%) and when taking BMI > 30 as the criterion for obesity (MD 0.06, 95% CI [0.00-0.12], I 2 = 76%). The occurrence of CKD did not differ when non-obese NAFLD were categorized into overweight and normal-weight types., Conclusions: Non-obese NAFLD patients experienced the same risk of CKD compared to obese NAFLD., Competing Interests: The authors declare that they have no competing interests., (© 2024 You et al.)

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder with no established pharmacotherapy. Quercetin, a polyphenolic flavonoid, demonstrates potential hepatoprotective effects but has limited bioavailability. This study evaluates the impact of quercetin on NAFLD and assesses the roles of autophagy-related proteins in disease progression. Methods: Forty-seven male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce NAFLD, followed by quercetin treatment for 4 weeks. Mice were divided into baseline, control, and two quercetin groups, receiving low (10 mg/kg) and high (50 mg/kg) doses. Liver histology was scored using the NAFLD Activity Score (NAS). Immunohistochemistry and immunoblotting were performed to analyze autophagy markers. Results: Quercetin-treated groups showed significant reductions in NAS compared to controls ( p = 0.011), mainly in steatosis and steatohepatitis. Immunohistochemistry indicated increased expression of autophagy markers LCA and p62 in quercetin groups. Western blot analysis revealed significant elevations in LC3A in the treated groups, suggesting improved autophagic activity and lipid degradation. Conclusions: Quercetin effectively reduces NAFLD severity and modulates autophagy-related proteins. These findings suggest that quercetin enhances autophagic flux, supporting its therapeutic potential for NAFLD. Additional research is needed to clarify the molecular mechanisms of quercetin and to determine the optimal dosing for clinical application.

Previous studies have reported an association between telomere length and non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the involvement of alternative lengthening of telomere-related genes (ALTRGs) in the pathology of NAFLD, construct a risk signature, and evaluate both treatment and prognosis. Three NAFLD datasets (GSE48452, GSE89632, and GSE63067) were collected from the GEO database and merged into combined GEO datasets. ALTRGs were collected from GeneCards and PubMed databases. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. This study employed a support vector machine algorithm and least absolute shrinkage and selection operator regression analysis to identify key genes for constructing a diagnostic model. High- and low-risk groups were identified from the combined GEO datasets using the diagnostic model. Gene set enrichment analysis, regulatory network analysis, and intergroup immune infiltration analysis were performed. This study identified the key genes using receiver operating characteristic and Friends analysis. Expression of these genes was validated in a mouse model of NAFLD. Twenty-five genes were differentially expressed, with a positive correlation between FOS and EGR1 and a negative correlation between MYC and CEBPA. A diagnostic model was constructed using 12 genes, and high- and low-risk groups were identified. CAMK2G, ERBB2, FOSB, WT1, and CEBPA showed certain accuracy, and their expression levels were significantly different in the model. Immune infiltration analysis between the risk groups revealed that six immune cells were statistically significant. This includes a strong negative interaction between type 2 T helper cells and SPHK2 in the high-risk group. These findings suggest that ALTRDEGs are potential therapeutic targets and prognostic indicators for NAFLD. However, further investigations are required to elucidate the specific underlying mechanisms., Competing Interests: Declarations. Ethics approval and consent for participation: The animal part of the study was approved by the Medical Ethics Committee of First Hospital of Qinhuangdao.We confirm that this study was reported in accordance with the ARRIVE guidelines ( https://arriveguidelines.org ). All experiments were performed according to relevant guidelines and regulations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases accompanied by lipid and glucose metabolism disorder. Didymin has been reported to have various hepatoprotective effects, however, its potential effects and mechanisms on NAFLD remain unclear from the perspective of the whole., Purpose: To investigate the underlying mechanism of didymin against NAFLD using multi-omics technologies., Methods: Rats were fed with a high-fat diet (HFD) for 8 weeks to induce NAFLD, followed by didymin treatment for 8 weeks. Next, biochemical analysis and histopathological examinations were performed to evaluate the effects of didymin. The key regulating pathways were predicted using transcriptomics, metabolomics and proteomics, and the target pathways were then verified by detecting the key genes/proteins using various experiments., Results: Didymin markedly mitigated liver injury and excessive lipid droplet accretion. An integrative multi-omics analysis suggested that the PPAR signaling cascade and insulin signaling pathway might serve as pivotal mechanisms underlying the modulation of lipid and glucose homeostasis by didymin. Further dissection identified five pivotal genes (PPARα, PPARβ, FABP4, ANGPTL4, and PLIN2) and four genes (HK1, HK3, GCK, and PTPN1) as potential hubs within these pathways. Subsequent validation experiments, including qPCR and Western blot, demonstrated upregulated expression of PPARα and PPARβ, indicating the activation of the PPAR pathway by didymin. Concurrently, didymin appeared to modulate the insulin signaling pathway, as evidenced by the upregulated expression of HK1 and downregulated expression of PTPN1. Notably, the manipulation of PPARα, PPARβ, and PTPN1 expression in LO2 cells through silence or overexpression confirmed that didymin significantly reduced lipid accumulation, with its molecular targets likely being the PPAR and insulin pathways., Conclusions: Our findings demonstrate that didymin has a protective effect on NAFLD, and its underlying mechanism may be associated with the regulation of the PPAR and insulin signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Backgroud: Non-alcoholic fatty liver disease (NAFLD) is a growing chronic liver disease worldwide, and no effective agent is approved yet for this condition. Traditional Chinese Medicine (TCM), which has been practiced for thousands of years in China and other Asian countries, is considered an important source for identifying novel medicines for various diseases. Miao medicine Yindanxinnaotong formula (YDX) is a classical TCM for the treatment of hyperlipidemia disease by reducing blood lipid content, while the role of YDX have not been clarified in NAFLD., Purpose: To investigate the protective effect of YDX on NAFLD in mice induced by high fat diet (HFD) and clarify the potential mechanism., Methods: NAFLD mice model was constructed by receiving HFD for 10-week period with or without YDX administration. Lipid profiles, biochemical indicators, and histopathological staining were performed to evaluate the extent of hepatic lipid accumulation and hepatic steatosis. 16S rRNA sequencing was used to determine the gut microbial composition. Serum metabolomics was further used to investigate the changes in plasma biomarkers for NAFLD-associated by UPLC-Q-TOF/MS analysis. Subsequently, liver transcriptomics was employed to identify differentially expressed genes and explore regulatory pathways. Then, lipid metabolism-related proteins and inflammation factors were examined by Western blot and ELISA., Results: YDX reduced body weight gain, liver index and inflammatory cytokines levels, along with improved hepatic steatosis, serum lipid profile, sensitivity to insulin and also tolerance to glucose, and enhanced oxidative defense system in HFD-induced mice. Also, YDX remarkedly affected gut microbiota diversity and community richness and decreased the ratio of Firmicutes/Bacteroidetes. Meanwhile, YDX also reduced the production of harmful lipid metabolites in the sera of NAFLD mice, such as LPC(18:0), LPC(18:1) and carnitine. Notably, consistent with liver transcriptomics results, YDX downregulated the expression of proteins implicated in de novo lipid synthesis (Srebp-1c, Acaca, Fasn, Scd-1, and Cd36) and pro-inflammatory cytokines (IL-6 and TNF-α), and increased the expression of proteins-related fatty acid β-oxidation (Ampkα, Ppar-α, and Cpt-1) in the liver by activating Ampk pathway., Conclusion: YDX is promisingly an effective therapy for preventing NAFLD by modulating the Ampk pathway, inhibiting gut microbiota disorder, and reducing the production of harmful lipid metabolites., Competing Interests: Declaration of competing interest The authors have no potential conflict of interest to disclose., (Copyright © 2024. Published by Elsevier GmbH.)

Gut microbiome dysbiosis is involved in non-alcoholic fatty liver disease (NAFLD) development. Hepatic transmembrane 4 L six family member 5 (TM4SF5) overexpression promotes NAFLD. However, how gut microbiota are associated with TM4SF5-mediated NAFLD remains unexplored. We analyzed the gut microbiome using feces from hepatocyte-specific TM4SF5-overexpressing transgenic (Alb-TG Tm4sf5 -Flag , TG) or Tm4sf5 -/- knock-out (KO) mice fed a normal chow diet (NCD), high-fat diet (HFD) for 2 weeks (HFD 2W ), or methionine-choline-deficient diet (MCD) for 4 weeks to investigate associations among Tm4sf5 expression, diet, and the gut microbiome. TG-NCD mice showed a higher Firmicutes-to-Bacteroidetes (F/B) ratio, with less enrichment of Akkermansia muciniphila and Lactobacillus reuteri. NASH-related microbiomes in feces were more abundant in TG-HFD 2w mice. Further, TG-MCD showed a higher F/B ratio than TG-NCD or KO mice, with decreases or increases in microbiomes beneficial or detrimental to the liver, respectively. Such effects in TG-MCD animals were correlated with functional pathways producing short-chain fatty acids (SCFAs). Furthermore, potential functional pathways of the gut microbiome were metabolically parallel to NAFLD features in TG-MCD mice. These results suggest that hepatocyte Tm4sf5 supports gut microbiome dysbiosis and metabolic activity, leading to SCFA production and hepatic inflammation during NAFLD development.2w mice. Further, TG-MCD showed a higher F/B ratio than TG-NCD or KO mice, with decreases or increases in microbiomes beneficial or detrimental to the liver, respectively. Such effects in TG-MCD animals were correlated with functional pathways producing short-chain fatty acids (SCFAs). Furthermore, potential functional pathways of the gut microbiome were metabolically parallel to NAFLD features in TG-MCD mice. These results suggest that hepatocyte Tm4sf5 supports gut microbiome dysbiosis and metabolic activity, leading to SCFA production and hepatic inflammation during NAFLD development., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Despite many recent studies on non-alcoholic fatty liver disease (NAFLD) therapeutics, the optimal treatment has yet to be determined. In this unfinished project, we combined secondary metabolites (SMs) from the gut microbiota (GM) and Hordeum vulgare (HV) to investigate their combinatorial effects via network pharmacology (NP). Additionally, we analyzed GM or barley - signalling pathways - targets - metabolites (GBSTMs) in combinatorial perspectives (HV, and GM). A total of 31 key targets were analysed via a protein-protein interaction (PPI) network, and JUN was identified as the uppermost target in NAFLD. On a bubble plot, we revealed that apelin signalling pathway, which had the lowest enrichment factor antagonize NAFLD. Holistically, we scrutinized GBSTM to identify key components (GM, signalling pathways, targets, and metabolites) associated with the Apelin signalling pathway. Consequently, we found that the primary GMs ( Eubacterium limosum , Eggerthella sp. SDG-2 , Alistipes indistinctus YIT 12060 , Odoribacter laneus YIT 12061 , Paraprevotella clara YIT 11840 , Paraprevotella xylaniphila YIT 11841 ) to ameliorate NAFLD. The molecular docking test (MDT) suggested that tryptanthrin-JUN is an agonist, conversely, dihydroglycitein-HDAC5, 1,3-diphenylpropan-2-ol-NOS1, and (10[(Acetyloxy)methyl]-9-anthryl)methyl acetate-NOS2, which are antagonistic conformers in the apelin signalling pathway. Overall, these results suggest that combination therapy could be an effective strategy for treating NAFLD.

Non-alcoholic fatty liver disease (NAFLD) has recently emerged as a challenging metabolic disorder with a strong emphasis on its prevention and management. Polyphenols, a group of naturally occurring plant compounds, have been associated with a decreased risk of various metabolic disorders related to NAFLD. The current systematic review aims to critically assess evidence about the ameliorative effect of polyphenol supplementation on NAFLD patients. A PRISMA systematic search appraisal was conducted in PubMed, Scopus, Web of Science Core Collection, and all relevant studies published prior to April 2024 and met the inclusion criteria were included. Twenty-nine randomized clinical trials (RCTs) comprised 1840 NAFLD patients. The studies primarily examined eleven phenolic compounds, including turmeric, curcumin, resveratrol, genistein, catechin, green tea extract, hesperidin, and silymarin. Turmeric and curcumin decreased liver enzymes, inflammatory cytokines, lipid profile, insulin resistance, and NAFLD score, while resveratrol did not present consistent results across all the studies. Most studies on silymarin showed a reduction in liver enzymes and lipid profile; however, no changes were observed in inflammatory cytokine levels. The dietary supplementation of hesperidin and naringenin or green tea extract caused improvements in liver enzyme, lipid profile, and inflammatory cytokine, while genistein supplementation did not modulate blood lipid profile. In conclusion, dietary supplementation of polyphenols could potentially prevent and ameliorate NAFLD. Still, the inconsistent results across the included RCTs require further clinical research to establish optimal dosage and duration.

Background: The relationship between dietary folate intake and prior mortality in adult patients with Non-alcoholic Fatty Liver Disease (NAFLD) has not been clearly studied. We aimed to examine the relationship between dietary folate intake and all-cause and cardiovascular (CVD) mortality in adult NAFLD patients in the US., Methods: Using data from National Health and Nutrition Examination Survey (NHANES) 2003-2018 and associated mortality data we conducted a cohort study of US adult NAFLD subjects. Multivariable Cox proportional hazards regression models were used to evaluate the relationship between dietary folate intake and both all-cause mortality and CVD mortality, accounting for potential confounders. The study employed restricted cubic spline analysis to investigate the non-linear association between dietary folate levels and mortality from all causes and cardiovascular disease., Results: Our final cohort consisted of 3,266 NAFLD patients, with a median follow-up of 10.3 years, 691 deaths were observed, including 221 cardiovascular deaths. Compared to participants with a folate intake in Quartile 1 (≤250 μg/d), those in Quartile 4 (≥467.5 μg/d) had multivariable-adjusted hazard ratios of 0.69 (95% CI, 0.51-0.94) for all-cause mortality (p for trend = 0.028) and 0.55 (95% CI, 0.29-1.04) for CVD mortality (p for trend = 0.107). A non-linear relationship between dietary intake and risk of death was not observed., Conclusion: Greater dietary folate intake is associated with a reduced risk of all-cause in American adults with NAFLD. Higher dietary folate intake not found to be associated with lower CVD mortality. These findings suggest that dietary folate may improve the prognosis of adult NAFLD patients. The measured-response relationship between dietary folate intake and mortality in patients with NAFLD requires further investigation., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Dong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In recent years, with the decline in HBV and HCV infections, there has been a corresponding reduction in both the morbidity and mortality of virus-associated HCC. Nevertheless, rising living standards, coupled with the increasing prevalence of metabolic disorders like diabetes and obesity, have led to a rapid surge in non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC) incidence. The mechanisms underlying the progression from NAFLD to NAFLD-HCC are multifaceted and remain incompletely understood. Current research suggests that genetic predisposition, metabolic dysregulation, lipotoxicity, oxidative stress, and inflammation are key contributing factors. Given the complexity of these mechanisms and the frequent occurrence of metabolic comorbidities like type 2 diabetes mellitus (T2DM) and cardiovascular disease in NAFLD-HCC patients, there is a pressing need for tailored therapeutic strategies, along with novel prevention, monitoring, and treatment approaches that are personalized to the patient's pathophysiology. Due to the limited depth of research, incomplete understanding of pathogenesis, and insufficient clinical data on NAFLD-HCC treatment, current therapeutic approaches largely rely on tumor staging. In this review, we synthesize current research on the pathogenesis, surveillance, diagnosis, treatment, and prevention of NAFLD-HCC, and offer perspectives for future studies, particularly regarding its underlying mechanisms.

The complex pathological mechanisms of non-alcoholic fatty liver disease (NAFLD) are closely related to dysregulated lipid metabolism, and the therapeutic effects of the traditional Chinese medicine Zexie-Baizhu Decoction (AA) on NAFLD have been gaining increasing attention. However, research into altered lipid metabolism, especially fatty acids, in NAFLD and the intervention of AA faces technical challenges, especially in the precise quantitative analysis of fatty acids in biological samples. The high complexity of biological matrices, particularly after drug intervention, greatly increases the difficulty of detection. Therefore, this study innovatively developed a simple and economical stable isotope derivatization technique by synthesizing d 6 N,N-dimethylethylenediamine (d 6 -DMED) in the laboratory, establishing a simple and economical method for fatty acid quantification. This method employs a chemical reaction under low-temperature conditions to ensure the efficient synthesis of d 6 -DMED. Using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry technique (UHPLC-MS/MS), combined with optimized chromatographic separation conditions and dynamic multiple reaction monitoring mode, the study established a highly sensitive detection method for 35 fatty acid derivatives. Methodological evaluation showed that the limits of quantification ranged from 0.002 to 0.060 μM, with high linearity of R² > 0.995. Additionally, the relative recovery rates were between 93.14% and 106.63%. To further demonstrate the feasibility of this method for fatty acid quantification, it was applied to measure fatty acids in multiple tissues in a mouse NAFLD model, as well as the effects of AA intervention on fatty acid metabolism. This rapid, simple, and cost-effective detection method not only enhances the understanding of NAFLD mechanisms but also provides a new strategy for evaluating the biological complex system after drug intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The recently discovered protein adropin is a highly conserved polypeptide that plays critical functions in energy homeostasis, metabolic processes, fat metabolism, and insulin resistance. On the other hand, non-alcoholic fatty liver disease (NAFLD) is a medical condition that causes the buildup of fat in the liver cells in individuals who consume little or no alcohol. The frequency of NAFLD is rising globally, and it is frequently linked to obesity, insulin resistance, type 2 diabetes, and metabolic syndrome. Therefore, this study evaluates the association between adropin levels and insulin resistance in individuals with and without NAFLD., Materials and Methods: Data from Scopus, Science Direct, and PubMed were searched between January 1, 2012, and February 18, 2024, using precise terms and stated criteria. Comprehensive Meta-Analysis V. 2 (Biostat, Englewood, NJ, USA) was used for data analysis, and Random-effect models were used to estimate the pooled mean differences with 95% CIs of adropin level, insulin level, and homeostatic model assessment for insulin resistance (HOMA-IR) associated with the exposures of interest., Results: Our results revealed that adropin blood levels are significantly reduced in NAFLD patients compared to control individuals. The mean difference in adropin blood levels was 2.391 ng/ml with a 95% CI of 1.127 to 3.656 with I2 99.6. on the other hand, insulin resistance was significantly higher in NAFLD compared to controls (MD: -1.668, 95% CI: -2.333 to -1.002, I2=86%)., Conclusions: Our findings reveal that adropin levels are significantly greater in healthy controls than in NAFLD patients, suggesting that adropin may have a preventative effect on NAFLD. This meta-analysis highlights how closely adropin and insulin resistance interact in non-alcoholic fatty liver disease. Also, it may open the door to new diagnostic tools and therapeutic modalities.