UNASSIGNED: At present, there is a dearth of comprehensive data at the global, national, and regional levels regarding the adult non-alcoholic fatty liver disease (NAFLD) prevalence. This cross-sectional study aims at ascertaining the prevalence of NAFLD and non-alcoholic steatohepatitis (NASH), utilizing body mass index (BMI) as a determining factor.
UNASSIGNED: Based on the NHANES database, sigmoidal fitting curves were generated to establish the relationship between BMI and the risk of NAFLD/NASH. Utilizing BMI data from the NCD Risk Factor Collaboration (NCD-RisC) database at both global and regional levels, the prevalence of NAFLD/NASH among adults was estimated from 1975 to 2016, encompassing global, regional, and national perspectives. Additionally, projections were made to forecast the prevalence of adult NAFLD/NASH from 2017 to 2030.
UNASSIGNED: In 2016, the global prevalence of NAFLD was 41.12% for males and 37.32% for females, while the global prevalence of NASH was 15.79% for males and 16.48% for females. The prevalence of NAFLD/NASH increased with higher BMI in both genders. Over the period from 1975 to 2016, there has been a gradual increase in the global prevalence of NAFLD/NASH in adults, and this trend is expected to continue between 2017 and 2030. In males, the prevalence of adult NAFLD/NASH was found to be highest in High-income Western countries, while it was highest in Central Asia, Middle East, and North African countries after 1995.
UNASSIGNED: The prevalence of adult NAFLD/NASH has been observed to increase annually, with significant variations in burden across different countries and regions.

Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome characterized by the excessive accumulation of fat within liver cells, which can progress to end-stage liver disease in severe cases, posing a threat to life. Pyroptosis is a distinct, pro-inflammatory form of cell death, differing from traditional apoptosis. In recent years, there has been growing research interest in the association between pyroptosis and NAFLD, encompassing the mechanisms and functions of pyroptosis in the progression of NAFLD, as well as potential therapeutic targets. Controlled pyroptosis can activate immune cells, eliciting host immune responses to shield the body from harm. However, undue activation of pyroptosis may worsen inflammatory responses, induce cellular or tissue damage, disrupt immune responses, and potentially impact liver function. This review elucidates the involvement of pyroptosis and key molecular players, including NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome, gasdermin D (GSDMD), and the caspase family, in the pathogenesis and progression of NAFLD. It emphasizes the promising prospects of targeting pyroptosis as a therapeutic approach for NAFLD and offers valuable insights into future directions in the field of NAFLD treatment.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) has become a significant health and economic burden globally. Yinchenhao decoction (YCHD) is a traditional Chinese medicine formula that has been validated to exert therapeutic effects on NAFLD.
OBJECTIVE: The current study aimed to explore the pharmacological mechanisms of YCHD on NAFLD and further identify the potential active compounds acting on the main targets.
METHODS: Compounds in YCHD were screened and collected from TCMSP and published studies, and their corresponding targets were obtained from the SWISS and SEA databases. NAFLD-related targets were searched in the GeneCards and DisGeNet databases. The \"compound- intersection target\" network was constructed to recognize the key compounds. Moreover, a PPI network was constructed to identify potential targets. GO and KEGG analyses were performed to enrich the functional information of the intersection targets. Then, molecular docking was used to identify the most promising compounds and targets. Finally, molecular dynamics (MD) simulations were performed to verify the binding affinity of the most potential compounds with the key targets.
RESULTS: A total of 53 compounds and 556 corresponding drug targets were collected. Moreover, 2684 NAFLD-related targets were obtained, and 201 intersection targets were identified. Biological processes, including the apoptotic process, inflammatory response, xenobiotic metabolic process, and regulation of MAP kinase activity, were closely related to the treatment of NAFLD. Metabolic pathways, non-alcoholic fatty liver disease, the MAPK signaling pathway, and the PI3K-Akt signaling pathway were found to be the key pathways. Molecular docking showed that quercetin and isorhamnetin were the potential active compounds, while AKT1, IL1B, and PPARG were the most promising targets. MD simulations further verified that the binding of PPARG-isorhamnetin (-35.96 ± 1.64 kcal/mol) and AKT1-quercetin (-31.47 ± 1.49 kcal/mol) was due to their lowest binding free energy.
CONCLUSIONS: This study demonstrated that YCHD exerts therapeutic effects for the treatment of NAFLD through multiple targets and pathways, providing a theoretical basis for further pharmacological research on the potential mechanisms of YCHD in NAFLD.

UNASSIGNED: Associations between metabolic risk factors and lung cancer remain elusive, and evidence on the linkage between non-alcoholic fatty liver disease (NAFLD) and pulmonary nodules is limited. This study sought to examine the independent association between NAFLD and the risk of pulmonary nodules.
UNASSIGNED: Cross-sectional analyses of 1,119 patients with intestinal polyps hospitalized at the Department of Gastroenterology, Minhang District Central Hospital of Shanghai, China, were conducted. NAFLD was diagnosed based on hepatic ultrasonography or computed tomography (CT) findings of hepatic steatosis, with exclusion criteria ensuring patients had no history of significant alcohol consumption, viral infections, or hepatic autoimmune diseases. The currently accepted definition of a pulmonary nodule is a solid or sub-solid shadow ≤3 cm in diameter that appears as a solid or semi-solid pattern on a chest CT scan (our specific treatment is pulmonary nodule size: 5 mm to 3 cm). Adjusted 95% confidence intervals (CIs) and odds ratios (ORs) for NAFLD and the clinical features connected with pulmonary nodule risk were determined using a multivariable logistic regression analysis.
UNASSIGNED: Among the 979 intestinal polyp patients, the prevalence rates of NAFLD and pulmonary nodules were 25.9% and 32.8%, respectively. Patients with pulmonary nodules exhibited higher rates of NAFLD (31.5% vs. 23.3%, P=0.006) and obesity (41.4% vs. 32.5%, P=0.006) compared to those without pulmonary nodules. After removing all the possible confounding variables, the adjusted ORs for NAFLD, an older age, smoking, and obesity were 1.370 (95% CI: 1.006-1.867, P=0.04), 1.022 (95% CI: 1.010-1.033), 1.599 (95% CI: 1.033-2.475), and 1.410 (95% CI: 1.057-1.880), respectively (all P values <0.05). NAFLD showed a significant association with an increased risk of pulmonary nodules.
UNASSIGNED: NAFLD was independently linked to an increased incidence of pulmonary nodules in intestinal polyp patients, which emphasizes the importance of screening and managing these conditions in lung cancer prevention.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) has become a worldwide public health problem. Current evidence on the association between dietary iron intake and the risk of NAFLD is limited. The present study aimed to investigate the associations of animal-derived dietary iron (ADDI) intake, plant-derived dietary iron (PDDI) intake, and the ratio of PDDI:ADDI with NAFLD risk among U.S. adult population.
METHODS: This was a repeated cross-sectional study. Data were collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. NAFLD was defined as a United States Fatty Lives Index ≥30, and dietary iron intake was assessed through two 24-h dietary recall in-terviews. Logistic regression and restricted cubic spline models were applied to examine the associations between dietary iron intake from different sources and NAFLD risk.
RESULTS: A total of 9478 participants aged ≥20 years were enrolled in the present study. After adjustment for multiple confounding factors, relative to the lowest quartile, the odds ratio (OR) and 95% confidence interval (CI) of NAFLD for the highest quartile was 1.01(95% CI, 0.82-1.24) for ADDI intake, 0.82 (95% CI, 0.64-0.99) for PDDI intake, and 1.00 (95% CI, 0.81-1.24) for the PDDI: ADDI intake ratio. In stratified analysis by sex and age, the significantly negative associations of PDDI intake with NAFLD was observed in women and participants older than 45 years. Dose-response analyses indicated that NAFLD was negatively associated with PDDI intake in a non-linear manner.
CONCLUSIONS: PDDI intake was negatively associated with NAFLD in U.S. adults.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by diffuse hepatocellular steatosis due to fatty deposits in hepatocytes, excluding alcohol and other known liver injury factors. However, there are no specific drugs for the clinical treatment of NAFLD. Therefore, research on the pathogenesis of NAFLD at the cellular and molecular levels is a promising approach to finding therapeutic targets and developing targeted drugs for NAFLD. Pin1 is highly expressed during adipogenesis and contributes to adipose differentiation, but its specific mechanism of action in NAFLD is unclear. In this study, we investigated the role of Pin1 in promoting the development of NAFLD and its potential mechanisms in vitro and in vivo. First, Pin1 was verified in the NAFLD model in vitro using MCD diet-fed mice by Western Blot, RT-qPCR and immunohistochemistry (IHC) assays. In the in vitro study, we used the oleic acid (OA) stimulation-induced lipid accumulation model and examined the lipid accumulation in each group of cells by oil red O staining as well as BODIPY staining. The results showed that knockdown of Pin1 inhibited lipid accumulation in hepatocytes in an in vitro lipid accumulation model and improved lipid indices and liver injury levels. Moreover, in vivo, WT and Pin1-KO mice were fed a methionine-choline deficient (MCD) diet for 4 weeks to induce the NAFLD model. The effects of Pin1 on lipid accumulation, hepatic fibrosis, and oxidative stress were evaluated by biochemical analysis, glucose and insulin tolerance tests, histological analysis, IHC, RT-qPCR and Western blot assays. The results indicate that Pin1 knockdown significantly alleviated hepatic steatosis, fibrosis and inflammation in MCD-induced NAFLD mice, improved glucose tolerance and alleviated insulin resistance in mice. Further studies showed that the AMPK/ACC1 signalling pathway might take part in the process by which Pin1 regulates NAFLD, as evidenced by the inhibition of the AMPK/ACC1 pathway. In addition, immunofluorescence (IF), coimmunoprecipitation (Co-IP) and GST pull-down experiments also showed that Pin1 interacts directly with ACC1 and inhibits ACC1 phosphorylation levels. Our study suggests that Pin1 promotes NAFLD progression by inhibiting the activation of the AMPK/ACC1 signalling pathway, and it is possible that this effect is achieved by Pin1 interacting with ACC1 and inhibiting the phosphorylation of ACC1.

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. Epidemiological studies have reported that exposure of the population to environmental endocrine-disrupting chemicals (EDCs) is associated with NAFLD. However, EDCs are of different types, and there are inconsistencies in the relevant evidence and descriptions, which have not been systematically summarized so far. Therefore, this study aimed to determine the association between population exposure to EDCs and NAFLD. Three databases, including PubMed, Web of science, and Embase were searched, and 27 articles were included in this study. Methodological quality, heterogeneity, and publication bias of the included studies were assessed using the Newcastle-Ottawa scale, I2 statistics, Begg\'s test, and Egger\'s test. The estimated effect sizes of the included studies were pooled and evaluated using the random-effects model (I2 > 50 %) and the fixed-effects model ( I2 < 50 %). The pooled-estimate effect sizes showed that population exposure to Phthalates (PAEs) (OR = 1.18, 95 % CI:1.03-1.34), cadmium (Cd) (OR = 1.37, 95 % CI:1.09-1.72), and bisphenol A (OR = 1.43, 95 % CI:1.24-1.65) were positively correlated with the risk of NAFLD. Exposure to mercury (OR =1.46, 95 % CI:1.17-1.84) and Cd increased the risk of \"elevated alanine aminotransferase\". On the contrary, no significant association was identified between perfluoroalkyl substances (OR =0.99, 95 % CI:0.93-1.06) and NAFLD. However, female exposure to perfluorooctanoic acid (OR =1.82, 95 % CI:1.01-3.26) led to a higher risk of NAFLD than male exposure. In conclusion, this study revealed that EDCs were risk factors for NAFLD. Nonetheless, the sensitivity analysis results of some of the meta-analyses were not stable and demonstrated high heterogeneity. The evidence for these associations is limited, and more large-scale population-based studies are required to confirm these findings.

Accumulating evidence from observational studies have suggested an association between gastroesophageal reflux disease (GERD) and non-alcoholic fatty liver disease (NAFLD). However, due to that such studies are prone to biases, we imported Mendelian randomization (MR) to explore whether the causal association between two diseases exsit. Hence, we aimed to analysis the potential association with MR. The single nucleotide polymorphisms (SNPs) of GERD were retrieved from the genome-wide association study dataset as the exposure. The SNPs of NAFLD were taken from the FinnGen dataset as the outcome. The relationship was analyzed with the assistance of inverse variance weighted, MR-Egger, and weighted median. We also uitilized the MR-Egger intercept, Cochran\'s Q test, leave-one-out analysis, MR-PRESSO, and Steiger directionality test to evaluate the robustness of the causal association. The meta-analysis were also implemented to give an overall evaluation. Finally, our analysis showed a causal relationship between GERD and NAFLD with aid of MR and meta-analysis (OR 1.71 95% CI 1.40-2.09; P < 0.0001).

BACKGROUND: The impacts of long-term exposure to air pollution on the risk of subsequent non-alcoholic fatty liver disease (NAFLD) among participants with type 2 diabetes (T2D) is ambiguous. The modifying role of Life\'s Essential 8 (LE8) remains unknown.
METHODS: This study included 23,129 participants with T2D at baseline from the UK Biobank. Annual means of nitrogen dioxide (NO2), nitrogen oxides (NOX), and particulate matter (PM2.5, PM2.5-10, PM10) were estimated using the land-use regression model for each participant. The associations between exposure to air pollution and the risk of severe NAFLD were evaluated using Cox proportional hazard models. The effect modification of LE8 was assessed through stratified analyses.
RESULTS: During a median 13.6 years of follow-up, a total of 1,123 severe NAFLD cases occurred. After fully adjusting for potential covariates, higher levels of PM2.5 (hazard ratio [HR] = 1.12, 95%CI:1.02, 1.23 per interquartile range [IQR] increment), NO2 (HR = 1.15, 95%CI:1.04, 1.27), and NOX (HR = 1.08, 95%CI:1.01, 1.17) were associated with an elevated risk of severe NAFLD. In addition, LE8 score was negatively associated with the risk of NAFLD (HR = 0.97, 95% CI: 0.97, 0.98 per point increment). Compared with those who had low air pollution and high LE8, participants with a high air pollution exposure and low LE8 had a significantly higher risk of severe NAFLD.
CONCLUSIONS: Our findings suggest that long-term exposure to air pollution was associated with an elevated risk of severe NAFLD among participants with T2D. A lower LE8 may increase the adverse impacts of air pollution on NAFLD.

Background: Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that has been reported as a potential treatment for non-alcoholic fatty liver disease (NAFLD). However, extensive phase II metabolism and poor aqueous solubility led to a decrease in the chrysin concentration in the blood after oral administration, limiting its pharmacological development in vivo. Methods: In the present study, we synthesized a novel chrysin derivative prodrug (C-1) to address this issue. We introduced a hydrophilic prodrug group at the 7-position hydroxyl group, which is prone to phase II metabolism, to improve water solubility and mask the metabolic site. Further, we evaluated the ameliorative effects of C-1 on NAFLD in vitro and in vivo by NAFLD model cells and db/db mice. Results: In vitro studies indicated that C-1 has the ability to ameliorate lipid accumulation, cellular damage, and oxidative stress in NAFLD model cells. In vivo experiments showed that oral administration of C-1 at a high dose (69.3 mg/kg) effectively ameliorated hyperlipidemia and liver injury and reduced body weight and liver weight in db/db mice, in addition to alleviating insulin resistance. Proteomic analysis showed that C-1 altered the protein expression profile in the liver and particularly improved the expression of proteins associated with catabolism and metabolism. Furthermore, in our preliminary pharmacokinetic study, C-1 showed favorable pharmacokinetic properties and significantly improved the oral bioavailability of chrysin. Conclusion: Our data demonstrated that C-1 may be a promising agent for NAFLD therapy.