Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and its prevalence has risen sharply. However, whether nutrition, dietary strategies, exercise, lifestyle and environment have preventive value for NAFLD remains unclear.

Through searching 4 databases (PubMed, Web of Science, Embase and the Cochrane Library) from inception to January 2025, we selected studies about nutrition, dietary strategies, exercise, lifestyle and environment in the prevention of NAFLD and conducted a narrative review on this topic.

Reasonable nutrient intake encompassing macronutrients and micronutrients have an independent protective relationship with NAFLD. Besides, proper dietary strategies including mediterranean diet, intermittent fasting diet, ketogenic diet, and dietary approaches to stop hypertension diet have their inhibitory effects on the developmental process of NAFLD. Moreover, right exercises including walking, jogging, bicycling, and swimming are recommended for the prevention of NAFLD because they could effectively reduce weight, which is an important risk factor for NAFLD, and improve liver function. In addition, embracing a healthy lifestyle including reducing sedentary behavior, not smoking, sleeping well and brushing teeth regularly is integral since it not only could reduce the risk of NAFLD but also significantly contribute to overall prevention and control. Finally, the environment, including the social and natural environments, plays a potential role in NAFLD prevention.

Nutrition, dietary strategies, exercise, lifestyle and environment play an important role in the prevention of NAFLD. Moreover, this review offers comprehensive prevention recommendations for people at high risk of NAFLD.

Exposure to diesel exhaust (DE) has been linked to an increased risk of various cancers, including liver cancer. However, the underlying mechanisms driving this association remain insufficiently understood. In this study, we employed a diethylnitrosamine (DEN)-induced mouse liver tumor model and conducted a 19-week combined exposure (750 μg/m3) using a DE exposure system. Our results demonstrated that long-term DE exposure activates cancer-related genes and enhances the formation of DEN-induced liver tumors. Compared to the DEN group, mice in the DEN + diesel exhaust exposure (DEE) group exhibited lower body weight, higher tumor formation rates and more severe DNA damage. The tumor-promoting effect of DE may be associated with the upregulation of SEMA4D and the activation of the PI3K/AKT signaling pathway. Additionally, liver cells in the DEE group exhibited nuclear atypia, a characteristic feature of cancerous transformation. In vitro studies have revealed that exposure to diesel exhaust particles (DEP) promotes the proliferation of HepG2 cells and HUH7 cells by upregulating SEMA4D and activating the PI3K/AKT signaling pathway. This effect was attenuated by inhibiting either SEMA4D or PI3K. This study was the first to identify that DE exposure promotes the development of DEN-induced liver tumors in mice, with the mechanism potentially involving the SEMA4D/PI3K/AKT pathway. These findings provide novel insights into the hepatotoxic effects of DE and highlight the need for further investigation into its carcinogenic potential.

Extreme heat and traffic-related air pollution (TRAP) have been linked to worsening chronic health disorders, however, their combined effects on diabetic nephropathy (DN) are little understood. Type II diabetic mice were exposed to heat (40 °C) and NO2 (5 ppm) separately for 4 h per day over 6 weeks to investigate the synergistic effects on the progression of DN. We found that exposure to high temperature and NO2 elevated blood glucose levels and exacerbated histopathological changes. Additionally, there were increased oxidation indicators (ROS, MDA, 8-OHdG) and decreased antioxidant indicators (CAT, SOD, GSH-PX), along with elevated inflammation markers (TNF-α, IL-1β, IL-6). The expressions of transient receptor potential (TRP) ion channels (TRPV1, TRPV4, TRPA1, TRPM2) were also upregulated. Our findings suggest that simultaneous exposure to high temperature and NO2 impairs metabolic and autophagy pathways. Exposure to both high temperature and NO2 produces a synergistic effect, leading to more severe damage than exposure to either factor individually. This resulted in increased expression of APOA1, P62, and p-mTOR/mTOR while decreasing the expression of p-AMPKα/AMPKα and LC3-II/I. This disruption promoted the progression of DN. In contrast, capsazepine (CZP) reduced TRP expression, inflammatory markers, oxidative stress, metabolic and autophagy disorders, thereby mitigating renal damage and alleviating the progression of diabetic nephropathy. Our study provides some potential strategies for early prevention and effective reduction of DN.

Our study aimed to explore the association between long-term exposure to low-dose ionizing radiation (LDIR) and dyslipidemia and its components among medical radiologists, and to identify the mediating role of inflammatory markers.

This cross-sectional study was conducted on 3918 medical radiologists, with data collected through questionnaires and occupational external exposure dosimeters. The multifactorial logistic regression and restricted cubic spline model were used to analyze the association between long-term exposure to LDIR and dyslipidemia and its components among medical radiologists, and mediation analysis was used to identify potential mediation effects.

Of 3918 medical radiologists, 995 (25.4 %) had dyslipidemia. The gender, age, body mass index (BMI), and smoking status were influential factors for dyslipidemia of medical radiologists. After adjusting for confounders, the OR and 95 % CI for the occurrence of dyslipidemia and high TG in the highest tertile group (Q3) were 1.32 (95 % CI: 1.04, 1.67) and 1.51 (95 % CI: 1.11, 2.07), respectively. Restricted cubic spline model showed that the cumulative effective dose was linearly associated with both dyslipidemia and high TG, and the risk of dyslipidemia and high TG increased with the cumulative effective dose. Mediation analysis suggested that the inflammatory marker SII significantly mediated the association between cumulative effective dose and TG levels.

Our study shows that medical radiologists have a high detection rate of dyslipidemia, and the risk of dyslipidemia and high TG increases with increasing cumulative effective dose. Inflammatory marker SII may play a mediating role in the association between cumulative effective dose and TG levels.

Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on steatotic liver disease limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver outcomes, and effect modification by folic acid (FA) supplementation in mother-child pairs.

We studied ∼200 mother-child pairs from the Mexican PROGRESS cohort, with 43 MDCs measured during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and organophosphate-pesticide metabolites), and serum liver enzymes (ALT, AST) at ∼9 years post-parturition. Outcomes included elevated liver enzymes in children and established clinical scores for steatosis and fibrosis in mothers (i.e.

ALT, FLI, HSI, FIB-4). Bayesian-weighted quantile sum regression assessed MDC-mixture associations with liver outcomes. We further examined chemical-chemical interactions and effect modification by self-reported FA supplementation.

In children, many MDC-mixtures were associated with liver injury. Per quartile HMWP-mixture increase, ALT increased by 10.1% (95% CI 1.67%, 19.4%) and AST by 5.27% (95% CI 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes were attenuated by maternal cobalt blood concentrations (p-interactions <0.05). In mothers, only the LMWP-mixture was associated with odds for steatosis (odds ratio = 1.53, 95% CI 1.01-2.28 for HSI >36, and odds ratio 1.62, 95% CI 1.05-2.49 for AST:ALT <1). In mothers and children, most associations were attenuated (null) at FA supplementation ≥600 μg/day (p-interactions <0.05).

Pregnancy MDC exposures may increase risk of liver injury and steatosis, particularly in children. Adequate FA supplementation and maternal cobalt levels may attenuate these associations.

The effects of environmental chemical exposures on steatotic liver diseases are not well understood. In a parallel investigation of mothers and children, we found that pregnancy exposures to metabolism-disrupting chemicals may increase the risk of liver injury and steatosis, especially in the child, and that these associations could be attenuated by higher folic acid and/or cobalt levels. These findings can inform policies to decrease environmental chemical pollution and contribute to the design of clinical interventions addressing the metabolic dysfunction-associated steatotic liver disease epidemic.

Ambient air pollution has been linked to neurodegenerative diseases. Nevertheless, the literature on the effects of air pollution on the olfactory system and early cognitive impairment is scarce. In this study, we investigated the association between long-term air pollution exposure and odor identification, which can serve as an early indicator of various neurodegenerative conditions. We used data collected in Augsburg, Germany in 2018-2019 for the population-based KORA FIT study of 3,059 participants born between 1945-1964. The Sniffin' Sticks 12-Item Test was used to assess each participant's odor identification. Air pollution concentrations at residential addresses were estimated using land use regression modeling. We dichotomized the odor identification score to normosmia (score ≥ 10) versus hyposmia (score < 7) or anosmia (score < 10) and applied logistic regression. The models were adjusted for age, sex, socioeconomic characteristics (education, income, socioeconomic status), lifestyle factors (physical activity, smoking, body mass index, alcohol consumption) and disease history (e.g., allergies). We observed increased odds of hyposmia or anosmia compared to normosmia per interquartile range increase in the concentrations of PNC, PM2.5, PM2.5abs, PMcoarse, PM10, NO2 and NOx [OR (95 % CI): 1.12 (1.02, 1.24), 1.10 (0.98, 1.25), 1.14 (1.00, 1.30), 1.20 (1.06, 1.35), 1.20 (1.06, 1.36), 1.20 (1.06, 1.37) and 1.13 (1.01, 1.27); respectively]. For O3, no clear effects were detected. Females and physically active people appeared to be more susceptible. No further significant indications of effect modification were found. The results were consistent across sensitivity analyses. This study provides robust evidence for an association between long-term exposure to traffic-related air pollution and poor odor identification, even in a region with relatively low air pollution levels. These findings suggest a potential link between prolonged air pollution exposure and early changes in the olfactory system and could be indicative of early signs of detrimental effects on the brain.

The incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) is high among U.S. adults, but studies on its occurrence in different ethnic and age groups are limited. The aim of the present study was to assess MAFLD occurrence among the U.S. adults by considering demographic characteristics, physical indices, and lifestyle conditions.

This study utilized the National Health and Nutrition Examination Survey (NHANES) data 2009-2018 from 23,546 participants aged ≥ 20 years. Variables such as age, sex, race, body mass index (BMI), waist circumference (WC), blood pressure, sedentary behavior, sleep, and depression were analyzed.

Among 9933 participants, 3562 had MAFLD (34.1%), with notably higher percentages of Mexican-Americans (54.1%) and lower percentages of blacks (20.5%). The incidence of MAFLD was significantly greater (P < 0.001) in males (39%) than in females (29.2%), which was particularly evident within the 36-40 years age group. The MAFLD incidence exhibited an age-dependent pattern, initially increasing and subsequently declining (except for whites). Compared to white MAFLD patients, black MAFLD patients exhibited greater BMI, WC, systolic blood pressure (SBP), and diastolic blood pressure (DBP) values, whereas values for these measures were lower among Mexican-American patients. Logistic regression analysis adjusting for age and sex revealed that depression was more common among MAFLD patients (P < 0.001), except for severe depression (P > 0.05). Notably, the MAFLD incidence was not significantly associated with sedentary behavior or sleep duration.

The MAFLD incidence varies across different racial, age, and sex groups, and targeted interventions are essential for reducing the burden of MAFLD. However, further research is necessary to explore the correlations among MAFLD incidence, sleep patterns, and an inactive lifestyle.

The continuum of metabolic syndrome encompasses a spectrum of dysfunctions impacting obesity-linked insulin resistance, glucose homeostasis, lipid metabolism and pro-inflammatory immune responses. The global prevalence of metabolic diseases, including diabetes, chronic liver disease, cardiometabolic disease and kidney disease, has surged in recent decades, contributing significantly to population mortality. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is a leading cause of liver disease worldwide. MASLD poses a significant global health challenge with its rising prevalence, placing a substantial burden on healthcare systems, impacts patient well-being and incurs significant economic costs. Addressing MASLD requires a comprehensive understanding of its interconnected factors, including its prevalence, healthcare burden and economic implications. Lack of awareness, imprecise non-invasive diagnostic methods and ineffective preventive interventions are core components of the MASLD-related problem.

The aim of this article was to summarise the global burden of MASLD from the payer's perspective.

We carried out a review of the global comprehensive burden of MASLD. These topics led to discussions and insights by an expert panel during the 7th Metabolic Continuum Roundtable meeting, which took place in November 2023. This meeting focused on the burden, patient-reported outcomes and health economics, from payor and societal perspectives, and aimed to identify opportunities for improving patient care, optimise resource allocation and mitigate the overall impact on individuals and society related to MASLD. During the roundtable, an emphasis emerged on the need for greater awareness and strategic deployment of diagnostic, therapeutic and preventative measures to address MASLD effectively.

The global burden of MASLD is high and growing. Prioritising the prevention of metabolic dysregulation and timely therapeutic interventions can yield a holistic strategy to combat MASLD, its progression and potentially lower disease costs.

NCT06309992.

Evidence regarding the role of acute kidney injury (AKI) in long-term development of metabolic dysfunction-associated fatty liver disease (MAFLD) is limited. We aimed to investigate the associations between AKI and liver-related events in patients with MAFLD.

This study involved 50,499 Chinese adults with MAFLD from the China Renal Data System (CRDS) database. We identified AKI using patient-level serum creatinine data according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The primary outcome was a composite of liver-related mortality and major adverse liver outcomes. The secondary outcome was an escalation of fibrosis-4 (FIB-4) risk scores. Cox proportional hazard models were performed to assess the association between AKI and the study outcomes.

The median age of the patients was 59.17 years, with 54.7% being male. There were 3,711 (7.3%) patients who experienced AKI during hospitalization. A total of 1,660 (3.3%) patients experienced composite liver outcome. Patients with AKI during hospitalization had higher risk of composite liver outcomes (adjusted hazard ratio (aHR) 1.83 [95% confidence interval 1.38;2.41] P < 0.001), especially among those with severe AKI (stage 2/3) (aHR 2.36 [1.57;3.54] P < 0.001). Regarding the secondary outcome, AKI was also associated with an increased risk of escalation of FIB-4 risk scores (aHR 1.28 [1.14;1.44] P < 0.001). These associations remained consistent across various subgroups and sensitivity analyses.

AKI was significantly associated with an increased risk of liver-related events among patients with MAFLD. These findings suggest that enhanced vigilance toward AKI may be justifiable in MAFLD patients.

Outdoor workers who are exposed to traffic-derived pollutants often suffer from a range of diseases, with liver disease being particularly notable. Recently, a rubber stabilizing additive antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its transformed-quinone product 6PPD-quinone (6PPD-Q) attracted attention. However, their implication for human health remains inadequately elucidated. In this study, outdoor and indoor workers were recruited to analyze 6PPD and 6PPD-Q distribution in their serum and urine. Simultaneously, blood cell counts, liver function, renal function, blood glucose level, and lipid profile were evaluated by 23 physiological parameters. For the first time, we found that the concentrations of 6PPD (0.54 - 1.66 μg L-1) and 6PPD-Q (0.58 - 4.04 μg L-1) in outdoor group serum were two- and three-fold in the indoor group, respectively. Compared with indoor workers, 18 biochemical parameters, notably total bilirubin and indirect bilirubin, were elevated in outdoor workers (p < 0.05). A computed tomography scan showed liver lesions in 60% of the outdoor group, whereas only 30% of the indoor group. The statistical analysis exhibited that significant positive correlations exist between the serum 6PPD-Q and immune cell counts, total bilirubin, indirect bilirubin, and triglycerides in human beings (p < 0.05). The logistic regression implied that for each 1 μg L-1 increase of 6PPD-Q in serum, the risk of human liver lesions increased by 2.31 times. Our results suggest that outdoor exposure is associated with increased concentrations of 6PPD-Q in serum, which could potentially influence glucose and lipid metabolism, immune cell regulation, and liver health.

The association between lifestyle and metabolic dysfunction-associated steatotic liver disease (MASLD) has been well documented. However, evidence is still limited from vulnerable populations, especially middle-aged and elderly adults with comorbid hypertension and diabetes, who are at higher risk of developing MASLD than the general population. We aimed to examine the potential causal links of a healthy lifestyle with the risk of MASLD in this vulnerable population.

A total of 41,964 middle-aged and elderly participants with comorbid hypertension and diabetes were included in a longitudinal cohort from 2010 to 2023. Weighted scores for lifestyle were evaluated by exercise frequency, alcohol consumption, smoking status and salt intake. Marginal structural models were used to estimate the single lifestyle-MASLD associations, which were further risk stratified by quartile ranges of weighted scores.

A mean follow-up period of 5.2 years (217 972 person-years) revealed that 21 697 participants developed MASLD. The hazard ratio (HR) of daily exercise, never consuming alcohol, never smoking and low salt intake for the risk of MASLD was 0.617 (95% confidence interval: 0.365 ~ 1.042), 0.237 (0.093 ~ 0.603), 0.153 (0.097 ~ 0.240) and 0.945 (0.919 ~ 0.971), respectively. Compared with weighted scores that were below the 25th percentile, the HR was 0.952 (0.902 ~ 1.005), 0.747 (0.694 ~ 0.803) and 0.097 (0.065 ~ 0.144) for the 25th, 50th and 75th percentiles, respectively.

In this vulnerable population, daily exercise, abstinence from alcohol and smoking and a low-salt diet may reduce the risk of MASLD, and the most stringent combination of healthy lifestyles could reduce the risk of MASLD by over 90%.

Air pollution is associated with advanced liver fibrosis in patients with chronic liver diseases, including chronic hepatitis B (CHB). This study aimed to investigate the association between air pollution and mortality in patients with CHB treated with nucleotide/nucleoside analogues.

We enrolled 697 patients with CHB treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for mortality. Daily air pollutant concentrations were estimated from the year before enrolment.

All-cause mortality showed an annual incidence of 1.1/100 person-years after a follow-up period of 3798.1 person-years. Factors with the strongest association with all-cause mortality were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.95/1.69-9.23; p = 0.02), age ([HR]/CI: 1.07/1.03-1.17, p < 0.001) and pre-treatment gamma-glutamyl transferase (GGT) levels (HR/CI: 1.004/1.001-1.006, p = 0.004). Among patients with cirrhosis, the factors associated with all-cause mortality were age (HR/CI: 1.08/1.04-1.12, p < 0.001), pre-treatment GGT levels (HR/CI: 1.004/1.001-1.008, p = 0.01), platelet count (HR/CI: 0.988/0.977-0.998, p = 0.02) and NOx concentration (per unit increment, ppb) (1.045/1.001-1.091; p = 0.046). The best NOx cut-off value for predicting all-cause mortality in patients with cirrhosis was 25.5 ppb (AUROC 0.63; p = 0.03). NOx levels > 25.5 ppb were associated with a higher incidence of mortality in patients with cirrhosis (HR/CI:2.49/1.03-6.02; p = 0.04).

Air pollution influences all-cause mortality in patients with CHB receiving nucleotide/nucleoside analogue therapy. Long-term NOx exposure may increase liver-related mortality in patients with chronic hepatitis B and cirrhosis receiving nucleotide/nucleoside analogue treatment.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), has become a pressing global health concern. The complexity of MASLD and the lack of universally effective treatments expose the limitations of current interventions, which focus mainly on lifestyle modifications. Here, we explore the multilayered nature of MASLD, emphasizing its pathophysiology in shaping future medical and lifestyle interventions from a personalized medicine perspective, based on individual molecular profiles. Additionally, we address the limitations of current animal models in reflecting human metabolic syndrome and sex-specific differences. We argue that a holistic approach, integrating social determinants of health, patient preferences, and adherence patterns, is essential for advancing MASLD management effectively.

Air pollution is a significant public health issue and an important risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), though the underlying mechanisms of this association are unknown. Herein, we aimed to identify metabolic signatures associated with exposure to ambient air pollution and to explore their associations with the risk of MASLD.

We utilized data from the UK Biobank cohort. Annual mean concentrations of PM2.5, PM10, NO2 and NOx were assessed for each participant using bilinear interpolation. The elastic net regression model was used to identify metabolites associated with four air pollutants and to construct metabolic signatures. Associations between air pollutants, metabolic signatures and MASLD were analyzed using Cox models. Mendelian randomization (MR) analysis was used to examine potential causality. Mediation analysis was employed to examine the role of metabolic signatures in the association between air pollutants and MASLD.

A total of 244,842 participants from the UK Biobank were included in this analysis. We identified 87, 65, 76, and 71 metabolites as metabolic signatures of PM2.5, PM10, NO2, and NOx, respectively. Metabolic signatures were associated with risk of MASLD, with hazard ratios (HRs) and 95% CIs of 1.10 (1.06-1.14), 1.06 (1.02-1.10), 1.24 (1.20-1.29) and 1.14 (1.10-1.19), respectively. The four pollutants were associated with increased risk of MASLD, with HRs (95% CIs) of 1.03 (1.01-1.05), 1.02 (1.01-1.04), 1.01 (1.01-1.02) and 1.01 (1.00-1.01), respectively. MR analysis indicated an association between PM2.5, NO2 and NOx-related metabolic signatures and MASLD. Metabolic signatures mediated the association of PM2.5, PM10, NO2 and NOx with MASLD.

PM2.5, PM10, NO2 and NOx-related metabolic signatures appear to be associated with MASLD. These signatures mediated the increased risk of MASLD associated with PM2.5, PM10, NO2 and NOx.

Air pollution is a significant public health issue and an important risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), however, the mechanism by which air pollution affects MASLD remains unclear. Our study used integrated serological metabolic data of 251 metabolites from a large-scale cohort study to demonstrate that metabolic signatures play a crucial role in the elevated risk of MASLD caused by air pollution. These results are relevant to patients and policymakers because they suggest that air pollution-related metabolic signatures are not only potentially associated with MASLD but also involved in mediating the process by which PM2.5, PM10, NO2, and NOx increase the risk of MASLD. Focusing on changes in air pollution-related metabolic signatures may offer a new perspective for preventing air pollution-induced MASLD and serve as protective measures to address this emerging public health challenge.

To investigate the association between air pollution and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues.

We enrolled 1298 CHB patients treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for HCC. Daily estimates of air pollutants were estimated since the previous year from the enrolment date.

The annual incidence of HCC was 2.1/100 person-years after a follow-up period of over 4840.5 person-years. Factors with the strongest association with HCC development were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.00/1.55-5.81; p = 0.001), male sex (2.98/1.51-5.90; p = 0.02), body mass index (1.11/1.04-1.18; p = 0.002) and age (1.06/1.04-1.09; p < 0.001). Among patients with cirrhosis, the factors associated with HCC development were male sex (HR/95% CI: 2.10/1.00-4.25; p = 0.04) and NO2 (per one-unit increment, parts per billion; 1.07/1.01-1.13; p = 0.01). Moreover, patients with the highest quartile of annual NO2 exposure had more than a three-fold risk of HCC than those with the lowest quartile of annual exposure (HR/95% CI: 3.26/1.34-7.93; p = 0.01). Among patients without cirrhosis, the strongest factors associated with HCC development were male sex (HR/95% CI: 5.86/1.79-19.23; p = 0.004), age (1.12/1.07-1.17; p < 0.001) and platelet count (0.99/0.98-1.00; p = 0.04).

Air pollution influences HCC development in CHB patients who receive nucleotide/nucleoside analogue therapy. Long-term NO2 exposure might accelerate HCC development in CHB patients with cirrhosis receiving nucleotide/nucleoside analogue treatment.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, and increasing evidence suggests that exposure to environmental pollutants is associated with the increased incidence of MASLD. The farnesoid X receptor (FXR) plays an important role in the development of MASLD by regulating bile acids (BAs) and lipid metabolism. However, whether FXR-active pollutants are the environmental drivers of MASLD remains unclear.

This study aimed to determine whether FXR-active pollutants exist in the environment and evaluate their ability to trigger MASLD development in mice.

An FXR protein affinity pull-down assay and nontargeted mass spectrometry (MS) analysis were used to identify environmental FXR ligands in sewage sludge. A homogeneous time-resolved fluorescence coactivator recruitment assay and cell-based dual-luciferase reporter assay were used to determine the FXR activities of the identified pollutants. Targeted analysis of BAs, MS imaging, lipidomic analysis, 16S rRNA sequencing, and quantitative polymerase chain reaction were conducted to assess the ability of FXR-active pollutants to induce metabolic disorders of BAs and lipids and to contribute to MASLD development in C57BL/6N mice.

We identified 19 compounds in the sewage sludge that had FXR-antagonistic activity, and triphenyl phosphate (TPHP) was the FXR antagonist with the highest efficacy. Mice exposed to either 10 or 50 mg / kg TPHP for 30 d had higher levels of conjugated primary BAs in enterohepatic circulation, and the BA pool showed FXR antagonistic activities. The exposed mice also had greater lipogenesis (more Oil Red O staining and high triglyceride levels) in liver.

Nineteen FXR-antagonistic pollutants were identified in sewage sludge. FXR inhibition by the strongest antagonist TPHP may have a role in promoting MASLD development in mice by inducing a positive feedback loop between the FXR and BAs. https://doi.org/10.1289/EHP15435.

The six-minute walk test (6MWT) is a key tool for assessing fitness in obese individuals, but existing reference equations for the six-minute walk distance (6MWD) are limited and overlook the six-minute walk work (6MWW), in turn limiting the clinical applicability of the test. This study aims to establish new 6MWD and 6MWW equations to improve our understanding of functional capacity in obese Chinese adults.

A cross-sectional study was conducted at Wenzhou People's Hospital from July 2021 to June 2023. Obese Chinese adults (BMI > 30 kg/m²), aged 18-69 years, completed the 6MWT following the ATS/ERS guidelines. Stepwise multiple regression was used to create sex-specific reference equations for the 6MWD and 6MWW.

A total of 309 obese Chinese adults participated in this study, achieving a mean 6MWD of 550.7 ± 45.85 m and a mean 6MWW of 46149.9 ± 6403.58 kg·m. Sex-specific equations for the 6MWD and 6MWW explained a significant portion of the variance in the values (34-61%).

The proposed reference equations for the 6MWD and 6MWW increase the accuracy and applicability of functional capacity assessment tests, outperforming existing reference equations. The inclusion of the 6MWW provides a relatively novel metric that integrates metabolic workload and mechanical efficiency, offering unique insights into the functional performance of obese individuals and allowing tailored health interventions.

Environmental pollutants significantly impact liver disease development, progression, and outcomes. This review examines the complex relationship between environmental exposures and liver pathology, from malignant conditions like hepatocellular carcinoma to steatotic and cholestatic liver diseases. Key environmental factors include air pollutants, volatile organic compounds, persistent organic pollutants, heavy metals, and per- and polyfluoroalkyl substances. These compounds can act through multiple mechanisms, including endocrine disruption, metabolic perturbation, oxidative stress, and direct hepatotoxicity. The impact of these exposures is often modified by factors such as sex, diet, and genetic predisposition. Recent research has revealed that even low-level exposures to certain chemicals can significantly affect liver health, particularly when combined with other risk factors. The emergence of exposomics as a research tool promises to enhance our understanding of how environmental factors influence liver disease. Importantly, exposure effects can vary by demographic and socioeconomic factors, highlighting environmental justice concerns. Implementation of this knowledge in clinical practice requires new diagnostic approaches, healthcare system adaptations, and increased awareness among medical professionals. In conclusion, this review provides a comprehensive examination of current evidence linking environmental exposures to liver disease and discusses implications for clinical practice and public health policy.

Herbal medicine has become an area of growing global scientific interest. The prime objective of this study was to investigate the protective role of Edgeworthia gardneri (Wall.) Meisn (EGM polysaccharide) against carbon tetrachloride (CCl4)-induced liver injury in mice. Forty-five ICR mice were randomly divided into three groups (n = 15): IC, IM, and IT. The IT group received EGM polysaccharide solution (50 mg/kg) daily, while the IC and IM groups were administered an equivalent volume of normal saline. The IT and IM groups were intraperitoneally injected with a mixture of CCl4 and olive oil at 1:1 (v/v) (2 mL/kg) every 3 days. Our results showed that EGM polysaccharide significantly (p < 0.05) reduced pathological hepatic alterations and an increased liver index caused by CCl4. Moreover, EGM polysaccharide therapy significantly (p < 0.001) increased levels of antioxidant enzymes, such as glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) and reduced malondialdehyde (MDA) content in a dose-dependent manner. Notably, EGM polysaccharide alleviated the inflammatory cascades as evidenced by decreased serum levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor- α (TNF-α) under CCl4 administration. Furthermore, 16 s rRNA gene sequencing results exhibited that EGM polysaccharide increased the abundance of probiotics bacteria, such as Unclassified_Lachnospiraceae, and decreased the abundance of pathogenic bacterial texas like Brevundimonas and Candidatus_Nitrocosmicu. Conclusively, EGM polysaccharide protects against CCl4-induced oxidative stress and inflammation in the liver and alleviates hepatic injury through beneficial gut microbiota modulations. The current study suggests that EGM polysaccharide is an effective agent in counteracting CCl4-induced hepatic damage.

Few studies have reported an association between intrahepatic cholestasis of pregnancy (ICP) and preconception exposure to PM2.5 and sunlight duration, but there has been no in-depth analysis of the correlation between ICP and different constituents of PM2.5. Thus, we performed this retrospective analysis among 160,544 pregnant women who delivered between 2014 and 2020, to further estimate the impact of different constituents of PM2.5, as well as the duration of sunlight, on ICP via generalized linear models. During the three months prior to conception, the adjusted odds ratios (aORs) for ICP were 1.176 (95 % CI: 1.066, 1.298) for a 10 μg/m3 increase in PM2.5, 1.080 (95 % CI: 1.026, 1.138) for a 1 μg/m3 increase in sulfate (SO42-), 1.069 (95 % CI: 1.025, 1.115) for a 1 μg/m3 increase in organic matter (OM), 1.274 (95 % CI: 1.049, 1.546) for a 1 μg/m3 increase in black carbon (BC), and 1.213 (95 % CI: 1.088, 1.353) for a 1-hour decrease in sunlight duration. In addition, during the preconception period, increased exposure to PM2.5 constituents (including SO42-, OM, and BC) and decreased sunlight duration interactively associated with ICP. Moreover, exposure to OM during the first trimester (aOR=1.043, 95 % CI: 1.004, 1.083) and to BC during both the first trimester (aOR=1.201, 95 % CI: 1.000, 1.442) and the second trimester (aOR=1.278, 95 % CI: 1.048, 1.558) were found to elevate the risk of ICP. In the future, women preparing to conceive should increase sunlight exposure and avoid exposure to air pollution, and the constituents related to anthropogenic emissions should be controlled to prevent these associations.

Climate change is the most important challenge of this century. Global surface temperature is continuously rising to new record highs, adversely affecting the health of the planet and humans. The purpose of this article is to review the impact of climate related environmental exposures on human health, healthcare delivery, and medical imaging and explore the potential to leverage medical imaging as a non-invasive tool to advance our understanding of climate related health effects. Radiology departments and healthcare systems must focus on building resilience to the effects of climate change while ensuring that the delivery of care is environmentally sustainable. Further research is needed to refine our understanding of the effects of climate change on human health and to forecast the expected changes in the demand for healthcare and radiology services.

Previous studies have shown that methyl tert-butyl ether (MTBE) could interfere with lipid metabolism. However, there is still a lack of epidemiological reports on the association between MTBE exposure and the risk of nonalcoholic fatty liver disease (NAFLD). In this study, a cross-sectional study was performed with data from the 2017-2020 cycles of the National Health and Nutrition Examination Survey (NHANES). The target population consisted of adults with reliable vibration controlled Transient elastography (VCTE) and blood MTBE concentration results. The hepatic steatosis and fibrosis were assessed by the values of the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. Generalized linear mixed model analysis was performed to evaluate the association between MTBE exposure and both steatosis and early liver fibrosis after adjustment for potential confounders. A total of 1303 subjects were enrolled and divided into NAFLD groups (CAP ≥ 248) and non-NAFLD groups (CAP < 248) based on the values of CAP in this study. Generalized linear mixed analysis suggested that blood MTBE concentration was positively associated with NAFLD risk in whole populations (OR: 2.153, 95% confidence interval [CI], 1.176-3.940) and female populations (OR: 11.019, 95% CI: 2.069-58.676). Blood MTBE concentration still showed an obvious positive correlation with the NAFLD risk after excluding factors such as diet and exercise in whole populations. Similarly, a positive correlation between blood MTBE concentration and liver fibrosis was also observed, although the results did not show significant statistical differences. In conclusion, our results indicate that MTBE exposure might be a potential important environmental pathogenic factor for NAFLD.

Hypertension development and progression are largely influenced by inflammation, which plays a critical role by activating the immune system and causing damage to the vascular endothelium. Metabolic dysfunction-associated fatty liver disease (MAFLD) is also associated with chronic low-grade inflammation, which drives disease progression via metabolic imbalances and adipose tissue dysfunction. This study investigates the relationship between inflammatory indices and MAFLD in hypertensive patients and assesses the predictive accuracy of these indices for MAFLD.

We performed a cross-sectional analysis involving 34,303 hypertensive patients from a Chinese hospital-based registry. The diagnosis of MAFLD was established using metabolic dysfunction criteria alongside evidence of hepatic steatosis confirmed through imaging. Complete blood counts were used to calculate inflammatory indices, including the monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and aggregate index of systemic inflammation (AISI). To assess the relationship between inflammatory indices and MAFLD, multivariable logistic regression was performed with adjustments for potential confounders. The diagnostic performance of these indices was analyzed using receiver operating characteristic (ROC) curves and area under the curve (AUC) calculations.

Patients with MAFLD exhibited significantly elevated levels of all inflammatory indices compared to those without. After multivariable adjustment, each standard deviation increase in AISI, SIRI, and SII was associated with a 74%, 62%, and 58% increased odds of MAFLD, respectively. The AUC for AISI was 0.659, indicating moderate diagnostic accuracy. The AUCs for SIRI and SII were 0.626 and 0.619, respectively, while NLR, PLR, and MLR had lower AUCs of 0.593, 0.558, and 0.589, respectively.

In hypertensive patients, inflammatory indices, especially AISI, show a strong association with MAFLD, indicating their potential utility in risk stratification within clinical settings. Further research is needed to evaluate the effectiveness of these markers in the management of MAFLD.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and air pollution are both significant health concerns. However, their combined effects on multi-system morbidity and all-cause mortality remain poorly understood.

We analyzed data from 434,417 UK Biobank participants, categorizing them into four groups: non-MAFLD, MAFLD-diabetes, MAFLD-lean, and MAFLD-overweight/obesity. To evaluate the long-term effects of air pollution exposure, we used time-varying Cox proportional hazard models to assess four air pollutants: particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5), PM10, nitrogen dioxide (NO2), and nitrogen oxides (NOx). We examined the associations between these air pollutants, MAFLD subtypes, and their joint impact on multi-system morbidity and all-cause mortality. Furthermore, we explored the additive and multiplicative interactions between air pollutants and MAFLD subtypes.

At baseline, 15,325 participants were classified as MAFLD-diabetes, 3341 as MAFLD-lean, and 140,934 as MAFLD-overweight/obesity. Among these groups, MAFLD-diabetes was most strongly associated with adverse outcomes compared to other subtypes. Air pollution exposure had a synergistic effect on cirrhosis risk across all MAFLD subtypes, with the most pronounced effects observed for PM2.5 [relative excess risk due to interaction (RERI): 2.10 (0.94, 3.26)] and NO2 [RERI:1.85 (0.67, 3.04)] in MAFLD-lean group. Positive additive and multiplicative interactions between air pollutants and MAFLD subtypes were also observed for coronary artery disease (CAD), with the exception of nitrogen oxide in the MAFLD-lean group. Additionally, only the MAFLD-diabetes demonstrated significant positive additive interactions with all four air pollutants in relation to chronic kidney disease (CKD).

This study highlights the distinct impacts of MAFLD subtypes on multi-system morbidity and all-cause mortality, underscoring the critical need for targeted prevention and treatment strategies, particularly for individuals with MAFLD-diabetes. Our findings reveal significant additive and synergistic effects of air pollution exposure on the risks of cirrhosis, CAD, and CKD among MAFLD patients.

Air pollution, especially particulate matter (PM), is one of the most common risk factors for global burden of disease. However, its effect on the risk of digestive diseases is unclear. Herein, we attempt to explore this issue by reviewing the existing evidence from published meta-analyses. We conducted a systematic literature search to identify all relevant meta-analyses regarding the association of air pollution with digestive diseases, and summarize their major findings. We assessed the methodological quality and evidence quality of the included meta-analyses using the AMSTAR-2 and GRADE tools, respectively, and the overlap of primary studies was assessed by the GROOVE tool. Nine meta-analyses were included in our analysis, containing 43 primary studies with high overlap. In the included meta-analyses, the methodological quality was from critically low to moderate, and the evidence quality was from very low to moderate. The exposure was primarily PM2.5. Seven, four, and one meta-analysis investigated the effect of air pollution on liver diseases, gastrointestinal diseases, and pancreatic diseases, respectively. PM2.5 exposure was significantly associated with liver dysfunction, chronic liver diseases, liver cancer, and colorectal cancer, but not oesophagus cancer, gastric cancer, or pancreatic cancer. Based on very low to moderate quality evidence from meta-analyses, PM2.5 exposure may contribute to the development of some digestive diseases, especially liver diseases.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition marked by excessive lipid accumulation in hepatic tissue. This disorder can lead to a range of pathological outcomes, including metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. Despite extensive research, the molecular mechanisms driving MASLD initiation and progression remain incompletely understood. Oxidative stress and lipid peroxidation are pivotal in the "multiple parallel hit model", contributing to hepatic cell death and tissue damage. Gut microbiota plays a substantial role in modulating hepatic oxidative stress through multiple pathways: impairing the intestinal barrier, which results in bacterial translocation and chronic hepatic inflammation; modifying bile acid structure, which impacts signaling cascades involved in lipidic metabolism; influencing hepatocytes' ferroptosis, a form of programmed cell death; regulating trimethylamine N-oxide (TMAO) metabolism; and activating platelet function, both recently identified as pathogenetic factors in MASH progression. Moreover, various exogenous factors impact gut microbiota and its involvement in MASLD-related oxidative stress, such as air pollution, physical activity, cigarette smoke, alcohol, and dietary patterns. This manuscript aims to provide a state-of-the-art overview focused on the intricate interplay between gut microbiota, lipid peroxidation, and MASLD pathogenesis, offering insights into potential strategies to prevent disease progression and its associated complications.

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.

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.

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 PM2.5, NOx, PM10, PM2.5-10, passive smoking, PM1, and air pollution from solid fuels were positively associated with the incidence and prevalence of NAFLD and its related cirrhosis. The risk ratios for PM2.5, NOx, PM10, PM2.5-10, 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 O3 was 0.75 (95 % CI: 0.69, 0.83), suggesting that O3 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 PM2.5 on NAFLD and its related cirrhosis. The results showed that the risk of NAFLD and its related cirrhosis associated with PM2.5 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.

The study findings show that PM2.5, NOx, PM10, PM2.5-10, passive smoking, PM1, and air pollution from solid fuels can increase an individual's risk of developing NAFLD and its related cirrhosis; while O3 can reduce the risk. In developing countries, the risk level of NAFLD and its related cirrhosis due to PM2.5 is higher than that in developed countries.

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 (PM2.5) and nitrogen dioxide (NO2), 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 PM2.5 and NO2. Cox proportional hazards models were applied to assess associations of PM2.5 and NO2 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, PM2.5 (hazard ratio [HR] = 2.57, 95%CI:1.27, 5.21, per ln increase) and NO2 (HR = 1.43, 95%CI: 1.10, 1.84, per ln increase) were positively associated with incident NAFLD. We identified 138 proteins associated with PM2.5 (92 positively, 46 inversely, FDR <0.05) and 143 with NO2 (100 positively, 43 inversely). Of the proteins that were significantly associated with both PM2.5 and NO2, 93 (79 positively, 14 inversely) and 79 (69 positively, 10 inversely) were significantly associated with incident NAFLD. Furthermore, 84 PM2.5-associated proteins and 66 NO2-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 PM2.5 and 2.6 % to 20.8 % for NO2, 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 PM2.5 and NO2 was associated with an increased risk of NAFLD partially by perturbating circulating proteins involved in pathways of inflammation and immunity responses.

Obesity, influenced by environmental pollutants, can lead to complex metabolic disruptions. This systematic review and meta-analysis examined the molecular mechanisms underlying metabolically abnormal obesity caused by exposure to a high-fat diet (HFD) and fine particulate matter (PM2.5). Following the PRISMA guidelines, articles from 2019 to 2024 were gathered from Scopus, Web of Science, and PubMed, and a random-effects meta-analysis was performed, along with subgroup analyses and pathway enrichment analyses. This study was registered in the Open Science Framework. Thirty-three articles, mainly case-control studies and murine models, were reviewed, and they revealed that combined exposure to HFD and PM2.5 resulted in the greatest weight gain (82.835 g, p = 0.048), alongside increases in high-density lipoproteins, insulin, and the superoxide dismutase. HFD enriched pathways linked to adipocytokine signaling in brown adipose tissue, while PM2.5 impacted genes associated with fat formation. Both exposures downregulated protein metabolism pathways in white adipose tissue and activated stress-response pathways in cardiac tissue. Peroxisome proliferator-activated receptor and AMP-activated protein kinase signaling pathways in the liver were enriched, influencing non-alcoholic fatty liver disease. These findings highlight that combined exposure to HFD and PM2.5 amplifies body weight gain, oxidative stress, and metabolic dysfunction, suggesting a synergistic interaction with significant implications for metabolic health.

Exposure to air pollution has been associated with increased dementia. However, it remains unknown what specific metabolic mechanisms play a role in this relationship. We included 192,300 dementia-free participants from the UK Biobank cohort study. Annual concentrations of air pollution were assessed based on the residential address. Elastic net regression was performed to identify air pollution-related metabolites, and metabolic score was constructed. Cox regression models and covariate balancing generalized propensity scores (CBGPS) regression models were conducted to explore the longitudinal associations between air pollution/metabolic signatures and dementia risk. The underlying mechanisms between air pollution and dementia driven by metabolic signature or specific metabolites were also investigated. A total of 2592 incident dementia cases were documented. We identified the metabolite profiles in response to air pollution exposure, including 87 metabolites for PM2.5, 65 metabolites for PM10, 76 metabolites for NO2, and 71 metabolites for NOx. The air pollution-related metabolic signatures were associated with increased risk of dementia, with hazard ratios (HR) of 1.17 (95 % CI: 1.12, 1.22), 1.06 (95 % CI: 1.02, 1.11), 1.16 (95 % CI: 1.10, 1.21), and 1.17 (95 % CI: 1.12, 1.22) for PM2.5, PM10, NO2 and NOx, respectively. The associations persisted using causal models. Metabolic signatures mediated the associations between air pollution exposure and dementia risk, with mediation proportions ranging from 6.57 % to 12.71 %. Additionally, we observed that a metabolite known as free cholesterol in medium VLDL (M-VLDL-FC) played a crucial mediating role. Our study provides novel insights into the metabolic mechanisms linking air pollution exposure to dementia risk.

Ambient fine particulate matter (PM2.5) is a significant contributor to air pollution. PM2.5 exposure poses a substantial hazard to public health. In recent years, the adverse effects of maternal PM2.5 exposure on fetal health have gradually gained public attention. As the largest organ in the body, the liver has many metabolic and secretory functions. Liver development, as well as factors that interfere with its growth and function, are of concern. This review utilized the adverse outcome pathway (AOP) framework as the analytical approach to demonstrate the link between maternal PM2.5 exposure and potential neonatal liver injury from the molecular to the population level. The excessive generation of reactive oxygen species (ROS), subsequent endoplasmic reticulum (ER) stress, and oxidative stress were regarded as the essential components in this framework, as they could trigger adverse developmental outcomes in the offspring through DNA damage, autophagy dysfunction, mitochondrial injury, and other pathways. To the best of our knowledge, this is the first article based on an AOP framework that elaborates on the influence of maternal exposure to PM2.5 on liver injury occurrence and adverse effects on liver development in offspring. Therefore, this review offered mechanistic insights into the developmental toxicity of PM2.5 in the liver, which provided a valuable basis for future studies and prevention strategies.