Search Results (2,074)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits, and excessive repetitive behaviors. While ASD has a strong genetic basis, growing evidence suggests that epileptic seizures may serve as environmental risk factors for ASD development. The high comorbidity between epilepsy and ASD (20–30%) suggests potential shared neurobiological mechanisms, yet the causal relationship remains poorly understood. To investigate the causal role of seizures in the development of ASD-like pathology, we exposed adolescent mice (3 weeks old) to electroconvulsive seizures (ECS) for 10 consecutive days. This repeated ECS exposure led to the emergence of autistic-like behaviors including significantly decreased sociability, increased repetitive self-grooming, enhanced marble burying behavior, and anxiety-like behaviors, without affecting general locomotor activity. Additionally, repeated exposure to ECS induced significant changes in glutamatergic neurotransmission in the mice’s prefrontal cortex and hippocampus, brain regions critically involved in social cognition and behavioral regulation. Interestingly, these changes occurred without alterations in other excitatory/inhibitory neuronal markers, suggesting a specific impact on glutamate receptor expression rather than a general disruption of excitatory/inhibitory balance. These findings suggest that repeated seizures may contribute to ASD-like symptoms by specifically affecting key glutamatergic neurotransmitter systems, providing insights into the neurobiological mechanisms underlying the comorbidity between epilepsy and autism. In addition, repeated ECS differentially regulated histone deacetylase (HDAC) transcripts in a region-specific manner and produced seizure-intensity-dependent transcriptomic signatures. Full article

Breast cancer (BRCA) possesses prominent molecular heterogeneity, where aberrant expression of genes annotated to asparagine metabolism networks drives malignant progression and therapeutic resistance. However, systematic construction of prognostic signatures from a holistic asparagine metabolic pathway perspective remains scarce, limiting the clinical translation of metabolic insights into prognostic tools. We integrated TCGA and GEO BRCA transcriptomic datasets to screen asparagine metabolism-related differentially expressed genes and build a prognostic model. Six biomarkers, SLC35A2, SRD5A2, NT5E, CEL, IFNG and CNR1, were selected via univariate Cox, LASSO and multivariate Cox regression. SRD5A2 and IFNG were enriched in low-risk patients, while the other four genes were upregulated in high-risk subgroups. This signature reliably stratifies patient prognosis, with risk scores correlating strongly with pathway activity, immune infiltration, immune checkpoints, mutation landscapes and drug responsiveness. Bioinformatic results were validated via TCGA cohort analysis, in vitro cellular assays and Western blot. Two in vivo models were established: 4T1 xenografts in 6-week-old BALB/c mice and DMBA/hormone-induced spontaneous breast tumors in 8-week-old SD rats. Tumors were generated by cell injection or DMBA gavage plus cyclic hormone treatment, and tissue sections were processed for immunohistochemistry. Consistent differential expression of the six core genes was validated across all in vitro and in vivo systems. In conclusion, this asparagine metabolism-associated signature offers candidate biomarkers for personalized prognosis and provides preclinical evidence for metabolism-targeted BRCA therapy. Full article

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a severe manifestation of lupus marked by cognitive and mood disorders, yet the molecular mechanisms underlying hippocampal dysfunction remain poorly understood. To address this, we performed bulk RNA sequencing on hippocampal tissue from 17-week-old female MRL/Lpr mice and MRL^+/+ controls, followed by an integrative multi-layered analytical workflow. Differential gene expression analysis identified 223 significant differentially expressed genes, with a predominant downregulation of myelin-related transcripts. Gene set enrichment analysis confirmed coordinated suppression of oligodendrocyte differentiation, neuron ensheathment, and Wnt signaling programs. Weighted gene co-expression network analysis identified a disease-associated module enriched in myelination and glial developmental pathways, with hub genes spanning structural, transcriptional, and adhesion-related functions. Cell-type deconvolution revealed a selective reduction in mature oligodendrocytes, while oligodendrocyte precursor cells remained largely unaffected, consistent with impaired lineage maturation rather than global loss. RT-qPCR and Western blot validated the repression of key myelin-related genes and MBP protein in MRL/Lpr hippocampi. Collectively, these findings challenge an inflammation-centric interpretation of NPSLE hippocampal pathology, highlighting instead an additional contribution of impaired oligodendrocyte maturation. This transcriptomic resource establishes a molecular foundation for future mechanistic and histological investigations. Full article

Neuroinflammation plays a central role in Alzheimer’s disease (AD). Glycyrrhizin (GL), a major component of licorice, exhibits anti-inflammatory effects, but its effects on AD pathology remain unclear. To investigate the effects of GL (18β-glycyrrhizin, 18β-GL) and its stereoisomer (18α-glycyrrhizin, 18α-GL) on cognitive function, neuroinflammation, and AD pathology in senescence-accelerated mouse prone 8 (SAMP8; P8) mice, 40-week-old P8 male mice, an AD model due to aging, and the control (senescence-accelerated mouse resistant 1, SAMR1; R1) mice were treated with 18β-GL, 18α-GL and physiological saline (control) for 12 weeks (n = 6 in each group). Cognitive function was evaluated using a step-through passive avoidance test. Plasma levels of α-Klotho, IGF-1, 2′,3′-cyclic GMP-AMP (2′,3′-cGAMP), HMGB1, IL-6, and TNF-α were measured by ELISA. Hippocampal microglial activation (Iba1), amyloid-β (Aβ) deposition, and phosphorylated tau (p-Tau) were assessed by immunohistochemistry. Aged P8 mice showed impaired memory, decreased α-Klotho and IGF-1 levels, and increased inflammatory markers compared with R1 mice. GL significantly improved memory performance, reduced inflammatory markers, and suppressed Iba1 activation, as well as Aβ and p-Tau accumulation. These effects were associated with inhibition of the cGAS–STING pathway, as indicated by reduced 2′,3′-cGAMP and HMGB1 levels. GL ameliorates AD pathology by inhibiting neuroinflammation, suggesting its therapeutic potential for AD. Full article

Butyl benzyl phthalate (BBP), a widely used endocrine-disrupting chemical, has been associated with reproductive toxicity; however, its long-term effects during aging remain poorly understood. In the present study, we examined the effects of prolonged BBP exposure on the male reproductive system using naturally aged C57BL/6J mice. Mice received BBP at 169 μg/kg/day in drinking water for 10 or 22 months and were analyzed at 24 months of age. No significant differences in body weight, food intake, or water consumption were observed among the experimental groups. Representative gross images showed apparent distension and dark-red discoloration of the seminal vesicles in BBP-exposed aged mice. Compared with Young mice, the BBP-exposed aged groups showed higher expression of IL-1β, IL-6, TNFα, SOD1, and SOD2 and lower CAT expression in the seminal vesicle. H₂DCFDA fluorescence showed a non-significant increasing trend. Because an untreated age-matched Old group was not included in the seminal vesicle analyses, the effects of aging and BBP could not be distinguished. In contrast, the testis showed limited changes in inflammatory cytokine-, antioxidant enzyme-, and steroidogenesis-related gene expression and in H₂DCFDA fluorescence relative to the untreated Old group. Exploratory miRNA sequencing of pooled testicular RNA and comparison with a TM3 Leydig cell dataset identified miR-664-5p as a candidate showing higher relative abundance in both datasets. TargetScan analysis predicted binding sites for miR-664-5p in FOXO1 and FOXO3. In BBP-treated TM3 cells, FOXO3 protein expression was decreased, and FOXO6 expression was increased, whereas FOXO1 showed no consistent dose-dependent change. These molecular findings do not establish direct regulation of FOXO proteins by miR-664-5p or explain the seminal vesicle findings. Full article

Background/Objectives: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulatory approach with potential therapeutic value for cognitive impairment in Alzheimer’s disease (AD). Ferroptosis-related oxidative injury has been implicated in AD-associated neuronal dysfunction, but whether rTMS-induced functional improvement is accompanied by changes in ferroptosis-related oxidative injury remains unclear. This study evaluated the effects of high-frequency rTMS on cognitive function, hippocampal neuronal excitability, and ferroptosis-related oxidative injury in amyloid precursor protein/presenilin-1 (APP/PS1) mice, using Ferrostatin-1 (Fer-1) as a pharmacological comparator. Methods: Six-month-old female mice were used, including age-matched C57BL/6J controls and APP/PS1 mice assigned to the AD + Sham, AD + rTMS, and AD + Fer-1 groups (n = 6 per group). After 14 days of intervention, cognitive performance was assessed using behavioral tests. Whole-cell patch-clamp recordings were performed in hippocampal dentate gyrus granule neurons to evaluate neuronal excitability and voltage-gated sodium (Na⁺) and potassium (K⁺) channel properties. Biochemical assays and transmission electron microscopy were used to assess oxidative, iron-related, and mitochondrial changes, and mitochondrial ultrastructure was examined in an independent cohort (n = 3 per group) using transmission electron microscopy. Results: Compared with AD + Sham mice, high-frequency rTMS improved cognitive performance, increased evoked action potential firing, lowered the elevated action potential threshold, partially restored voltage-gated Na⁺ and K⁺ current amplitudes, and accelerated recovery of Na⁺ currents from inactivation. Fer-1 produced partially overlapping, but not identical, effects across behavioral, electrophysiological, biochemical, and ultrastructural outcomes. Both interventions increased hippocampal glutathione (GSH) levels, reduced malondialdehyde (MDA) and total iron levels, partially restored superoxide dismutase (SOD) activity, and improved mitochondrial ultrastructure and reduced the prevalence of mitochondrial profiles with small cross-sectional areas. Conclusions: High-frequency rTMS improved cognitive and hippocampal neuronal outcomes in female APP/PS1 mice. These improvements were accompanied by biochemical and mitochondrial changes compatible with attenuation of ferroptosis-related injury. However, the findings do not establish ferroptosis inhibition as either necessary or sufficient for the effects of rTMS. Full article

To investigate the patterns of cadmium accumulation and distribution in mice following oral ingestion of cadmium-enriched Portunus trituberculatus, this study selected 4-week-old ICR mice as a model organism. A control group was fed a standard diet, while an exposure group was fed a diet supplemented with 10% cadmium-enriched Portunus trituberculatus. After 28 consecutive days of exposure, the mice were switched to a standard diet for 7 days. Tissues and feces were collected throughout the experiment; cadmium levels were determined by inductively coupled plasma mass spectrometry (ICP-MS) following microwave digestion. The results showed that after 28 days of exposure, cadmium accumulation was observed in the kidneys (females: 0.046 ± 0.001 mg/kg, males: 0.053 ± 0.005 mg/kg) and livers (females: 0.046 ± 0.008 mg/kg, males: 0.034 ± 0.001 mg/kg), while levels in the control group were below the limit of detection; After a subsequent 7-day period of feeding standard diet, cadmium accumulation was observed in the kidneys (females: 0.070 ± 0.001 mg/kg, males: 0.047 ± 0.006 mg/kg), livers (females: 0.040 ± 0.001 mg/kg, males: 0.035 ± 0.009 mg/kg), and the intestines (females: 0.028 ± 0.006 mg/kg, males: 0.029 ± 0.001 mg/kg) still contained trace amounts of cadmium that had not been excreted. An apparent mass balance analysis suggested that more than 90% of ingested Cd was not retained in the analyzed tissues. In summary, although cadmium ingested orally is primarily excreted, the clearance rate for cadmium accumulated in the liver and kidneys of mice is relatively low, and residual levels remain in the tissues even 7 days after exposure ceased, indicating that even when the majority of ingested Cd is eliminated, the fraction retained in target organs may persist after exposure cessation and warrants further investigation under longer-term exposure scenarios. Full article

Introduction: Mechanical loading has been shown to accelerate bone growth in healthy mice, but if this is the case also in growth suppressed animals with an inflammatory condition remains unexplored. To address this, we explored the potential for mechanical loading to stimulate longitudinal bone growth under conditions of chronic inflammation. Methods: A transgenic mouse model overexpressing human tumor necrosis factor (huTNFTg) was used to mimic chronic inflammation. Six-week-old animals were exposed to daily mechanical loading, applied laterally to the right knee joint, 5 times per week for 4 weeks while bone growth was monitored weekly. The contralateral side was sham-loaded and served as an internal control. At the endpoint, growth plate morphology was assessed. For mechanistic studies, fetal rat femur bones were cultured ex vivo with cytokines added for 12 days while mechanical loading was applied every 2–3 days. Results: Mechanical loading stimulated femur bone growth, not only in wild-type controls but also in huTNFTg mice. Growth plate morphometric analyses revealed reduced growth plate height and hypertrophic zone heights in huTNFTg mice, and mechanical loading was able to counteract these changes. Ex vivo studies in cultured femur bones showed that mechanical loading can partially prevent cytokine-induced bone growth suppression, suggesting that the effect is locally mediated, rather than systemically. Conclusions: Our in vivo and ex vivo data showed that mechanical loading locally stimulates bone growth even when exposed to inflammatory cytokines. These findings suggest that mechanical loading may have a beneficial role in regulating bone growth under chronic inflammatory conditions. Full article

Background: Zearalenone (ZEN) exposure poses health risks to both humans and animals. Although evidence indicates that ZEN significantly impairs oocyte developmental competence, the underlying mechanisms remain largely unclear. While it is recognized that prepubertal animals are particularly vulnerable to ZEN and that juvenile in vitro embryo transfer represents a promising strategy for accelerating genetic progress, the potential impact of ZEN on developmental competence of prepubertal oocytes remains uninvestigated. Methods: In vivo, we administered graded oral doses of ZEN to female mice at prepubertal (3 weeks), peripubertal (6 weeks), and post-pubertal (8 weeks) stages and assessed oocyte developmental potential and related markers and ZEN residues in ovaries and livers following superovulation. In vitro, oocytes isolated from mice of each age group were subjected to graded ZEN concentrations during in vitro maturation, followed by evaluation of oocyte developmental potential. Results: This study shows that oral ZEN exposure impairs oocyte developmental competence and cumulus expansion, and disrupts oocyte redox homeostasis, mitochondrial integrity and glutathione biosynthesis in a mouse age-specific manner, with prepubertal (3-week-old) mice exhibiting the greatest susceptibility. Assessment of systemic ZEN disposition shows that ZEN concentrations in both ovarian and hepatic tissues were significantly higher in 3-week-old mice than in 6- and 8-week-old mice. Furthermore, exposure of oocytes to graded ZEN concentrations during in vitro maturation demonstrate that oocytes from prepubertal mice exhibit intrinsically heightened susceptibility to ZEN-induced functional deficits relative to those from sexually mature adults. Conclusions: This study demonstrates that ZEN exposure compromises oocyte developmental competence in a host age-dependent manner, and the heightened vulnerability in prepubertal oocytes is associated with both increased ovarian ZEN bioavailability and their intrinsically greater sensitivity to ZEN. Full article

Background/Objectives: This study aimed to investigate the effects of oral Bacillus subtilis (BS) on alveolar bone loss, intestinal morphology, and gut microbiota in a mouse model of ligature-induced periodontitis. Methods: A total of 24 male C57BL/6J mice (6 weeks old) were allocated to control, periodontitis (P), BS, and BS+P groups. Periodontitis was induced by bilateral ligation of maxillary second molars, and BS was orally administered for 18 consecutive days. Gut microbiota composition was analyzed by 16S rDNA sequencing, alveolar bone loss and gut morphology were evaluated using ImageJ version 1.54g, and ELISA-detectable serum vitamin D metabolite concentrations were measured using an enzyme-linked immunosorbent assay. Results: Compared with the P group, the BS+P group showed reduced bone loss. Serum vitamin D metabolite concentrations, small-intestine villus height, and villus height-to-crypt depth ratios were higher in the BS+P group. In gut microbiota, alpha diversity differed significantly among groups based on the Shannon index. Bray–Curtis-based beta diversity differed significantly among groups. Conclusions: Oral supplementation of BS attenuated the progression of ligature-induced periodontitis in a mouse model, and changes in gut microbiota may be associated with this effect. Full article

Objectives: The purpose of this study was to investigate the protective effects and underlying mechanisms of fucoidan on contrast-induced acute kidney injury (CI-AKI) in mice, focusing on the TLR4/NF-κB and Nrf2/GPX4 pathways. Methods: Five-week-old male ICR mice were randomly divided into normal control, contrast model, low-dose (100 mg/kg), and high-dose (300 mg/kg) fucoidan groups. Renal index, biochemical markers, histopathology, oxidative stress indicators, inflammatory cytokine levels, and the expression of TLR4/NF-κB, Nrf2/HO-1, and ferroptosis-related proteins were assessed. Untargeted metabolomics followed by KEGG pathway enrichment was also performed. Results: Our results showed that contrast successfully established the CI-AKI model, as evidenced by an increased kidney index, abnormal biochemical parameters, severe renal pathological damage, oxidative stress imbalance, inflammatory activation, ferroptosis, and metabolic disturbances. Fucoidan dose-dependently improved kidney index and biochemical markers, alleviated pathological injury, enhanced antioxidant capacity, suppressed inflammation and ferroptosis, and reversed metabolic pathway disorders (e.g., purine and glycerophospholipid metabolism), with the high dose showing more pronounced effects. Conclusions: Fucoidan could effectively ameliorate CI-AKI, and its effects are closely associated with the inhibition of the TLR4/NF-κB pathway, activation of the Nrf2/HO-1 pathway, regulation of ferroptosis-related proteins, and improvement of key metabolic disturbances, suggesting a new research direction for the prevention of CI-AKI. Full article

Aim: To establish and validate a quantitative transporter-mediated imaging framework based on gadoxetic acid-enhanced T1 mapping for assessing liver functional reserve (LFR) and to investigate the physiological significance of the relative change in longitudinal relaxation rate (ΔR1%) as a quantitative imaging biomarker. Methods: Female C57BL/6J mice (6–8 weeks old) representing five experimental liver conditions (control, transporter-deficient Slco1b2/Slco1a5 double-knockout, carbon tetrachloride-induced fibrosis, methionine–choline-deficient diet-induced steatohepatitis, and alcohol-associated fatty liver disease; n = 6 per group) underwent serial Gd-EOB-DTPA-enhanced T1 mapping. Quantitative ΔR1% was calculated to characterize hepatobiliary enhancement kinetics. Liver functional reserve was independently evaluated using multispectral optoacoustic tomography of indocyanine green (ICG) pharmacokinetics and serum ICG retention assays, with histopathological and hepatocellular transporter analyses performed for mechanistic validation. Longitudinal data were analyzed using restricted maximum likelihood (REML)-based mixed-effects models. Intergroup comparisons were performed using one-way ANOVA or Kruskal–Wallis tests with appropriate post hoc analyses, and associations between imaging and functional parameters were evaluated using Spearman rank correlation analysis. A two-sided p < 0.05 was considered statistically significant. Results: Five experimental liver models exhibited distinct transporter-dependent hepatobiliary enhancement patterns. The transporter-deficient knockout mice showed minimal enhancement, whereas fibrosis and steatotic liver injury models demonstrated intermediate but clearly distinguishable functional profiles. Longitudinal mixed-effects analysis identified significant effects of time, experimental group, and time-by-group interaction on ΔR1% dynamics (all p < 0.0001). Although MRI-derived ΔR1% parameters were not significantly correlated with regional optoacoustic ICG kinetics, ΔR1% area under the curve showed a strong inverse correlation with serum ICG retention at 600 s (r = −0.729, p < 0.0001), indicating that MRI-derived ΔR1% and ICG-based measurements provide complementary rather than interchangeable assessments of liver function. Histological and molecular analyses further demonstrated marked heterogeneity in fibrosis, steatosis, and hepatobiliary transporter expression across models, whereas transporter abundance alone did not consistently predict imaging-derived functional performance. Conclusions: Quantitative Gd-EOB-DTPA-enhanced T1 mapping provides a transporter-mediated imaging framework for evaluating hepatic functional reserve across mechanistically distinct liver injury models. As a normalized quantitative imaging biomarker, ΔR1% captures the integrated functional consequences of hepatobiliary transport dysfunction and complements established liver function tests. These findings support the translational potential of quantitative T1 mapping as a standardized, noninvasive approach for assessing liver functional reserve. Full article

Objectives: This study aimed to investigate the mechanisms underlying impaired sperm motility in high-fat diet (HFD)-induced obesity. Methods: Six-week-old male C57BL/6J mice were used to establish an HFD-induced obesity model. Sperm motility and male reproductive function were then evaluated. Macrophage polarization was evaluated by flow cytometry, and key differentially expressed genes were identified by RNA-seq analysis of epididymal adipose tissue, the epididymis, and testes. Finally, pyruvate carboxylase (PC) and the PC inhibitor erianin (Eri) were used to examine the role of adipocyte-derived PC in regulating macrophage polarization. Results: HFD-induced obese mice exhibited abnormal testicular and epididymal morphology, with reduced sperm motility and viability. Flow cytometry revealed that macrophages were polarized toward the M1 phenotype in epididymal adipose tissue and the epididymis in the HFD group. RNA-seq analysis demonstrated that PC was the most significantly upregulated gene in epididymal adipose tissue. Furthermore, PC expression increased during adipocyte maturation in vitro. Mature adipocytes promoted macrophage polarization toward the M1 phenotype, while Eri attenuated this effect. In addition, supernatants from LPS-induced M1 macrophages contained elevated levels of inflammatory cytokines and significantly reduced sperm motility and viability. Conclusions: HFD-induced obesity impaired sperm quality and male reproductive function. The underlying mechanism may involve increased PC expression, which drives epididymal macrophages toward M1 polarization and triggers local chronic inflammation, ultimately compromising sperm motility and viability. Full article

Corneal endothelium is a single layer of polygonal cells responsible for maintaining stromal dehydration and corneal transparency. Isolating corneal endothelium from murine models is exceptionally challenging without an established protocol, which historically limits the utility of mouse models to study corneal endothelial disease. Herein, a detailed method is presented to obtain a highly pure population of corneal endothelial cells via mechanical peeling of the endothelial sheet from both young and aged mice. Under a dissecting microscope, the corneal dome, including the limbus, was dissected. Following the removal of the iris and trabecular meshwork, the corneal dome was rinsed in phosphate-buffered saline (PBS). Fine, blunt forceps were utilized to stabilize the edge of the corneal dome, while ultra-fine forceps were employed to grasp the edge of Descemet’s membrane (DM). The edge of the DM was identified by performing a gentle micro-scratch along the limbal margin until a small flap emerged. Subsequently, the entire endothelial sheet along with the DM was carefully peeled from the periphery toward the corneal center. The isolated endothelial sheet can be dried flat on a microscope slide to investigate spatial gene expression, cell morphology, and cellular interactions. To obtain a single-cell suspension, the endothelial sheet was enzymatically digested in 0.25% Trypsin-EDTA for 8 min at 37 °C, yielding a highly purified population of corneal endothelial cells (95.7%). This protocol demonstrated high reproducibility for both young (approximately 1 month old) and aged (approximately 1 year old) mouse corneas. The total cell yields collected from young and old mice were 3634 and 4560 cells per eye, respectively, exhibiting high cell viability (young: 98.3%, old: 95.8%) and a high percentage of single cells (young: 90.6%, old: 90.1%). This detailed isolation protocol will facilitate advanced downstream research on the corneal endothelium using murine models. Full article

Background and Purpose: Ultra-processed food (UPF) intake is a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD) development, and fibroblast growth factor 21 (FGF21) is a key regulator of hepatic lipid metabolism, but its role in this association remains unclear. We aimed to investigate whether FGF21 mediates the UPF-MASLD relationship in a population-based cohort and whether berry extract (BE) protects against UPF-related liver injury through FGF21 signaling. Methods: This study included 29,386 participants with magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) and iron-corrected T1 (cT1) from the UK Biobank. UPF intake was classified according to the NOVA system. Log-binomial and generalized linear regression models were used to estimate the associations of UPF with MASLD, PDFF, and cT1, respectively. In vivo, nine-month-old male C57BL/6J mice were fed a baked Western diet (BWD) with bilberry extract (BE, 200 mg/kg/day) or vehicle for 16 weeks. In vitro, the role of FGF21 was examined by knockdown experiments in AML12 hepatocytes. Results: UPF consumption was linearly associated with a higher risk of MASLD, with per 10% increment associated with 9% higher risk of MASLD (RR 1.09 [95% CI 1.07–1.10]), as well as dose-dependent increases in PDFF and cT1. Among the 283 plasma proteins associated with PDFF, FGF21 showed the strongest association with UPF intake and accounted for the largest proportion of mediation in the UPF-PDFF association. A significant interaction between UPF and berry intake was observed in MASLD risk (p for interaction = 0.018). In the animal model, BE supplementation for 16 weeks alleviated BWD-induced hepatic steatosis, inflammation, and glucose intolerance, while upregulating hepatic FGF21, FGFR1c, and β-Klotho expression and improving mitochondrial function. FGF21 knockdown abrogated BE’s protective effect against lipid accumulation in vitro. Conclusions: FGF21 emerged as a potential mediator of the association between UPF consumption and liver fat accumulation. Anthocyanin-rich dietary interventions may offer a promising strategy to prevent MASLD progression. Full article