Search Results (190)

Introduction/Objectives: Ginsenoside F1, a pharmacologically active saponin derived from Panax ginseng, exhibits diverse bioactivities, but its use is limited because it is difficult to purify and has high production costs. To overcome these challenges, a ginsenoside F1-enriched extract named SGB121 was developed. This study aimed to evaluate the therapeutic efficacy of SGB121 in a high-fat, high-carbohydrate (HFHC) diet-induced metabolic dysfunction-associated fatty liver disease (MAFLD) mouse model and to elucidate its mechanism of action using F1-based cellular assays. Methods: Male C57BL/6 mice (6 weeks old) were fed an HFHC diet to induce MAFLD and were treated with SGB121. Hepatic lipid accumulation, oxidative stress markers, and metabolic parameters were analyzed. In parallel, human hepatocellular carcinoma (HepG2) cells exposed to free fatty acids (FFAs) were used to assess oxidative stress and lipid accumulation. Mechanistic studies were conducted using purified F1 to examine adenosine monophosphate-activated protein kinase (AMPK) activation and related pathways. Results: SGB121 reduced hepatic lipid accumulation, malondialdehyde (MDA) levels, and fasting insulin while restoring glutathione (GSH) content and improving the homeostasis model assessment of insulin resistance (HOMA-IR) in MAFLD mice. In FFA-treated HepG2 cells, both SGB121 and F1 decreased reactive oxygen species (ROS), suppressed sterol regulatory element-binding protein 1 (SREBP1), enhanced peroxisome proliferator-activated receptor-α (PPARα) and β-oxidation, and restored insulin receptor substrate (IRS)/protein kinase B (Akt)/glucose transporter 2 (GLUT2) signaling. Conclusions: SGB121 ameliorates MAFLD and related metabolic dysfunction through antioxidant, lipid-regulating, and insulin-sensitizing actions, highlighting its potential as a safe multifunctional nutraceutical for MAFLD management. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic hepatic disease with a rising global prevalence (25–38% of the general population). As a new term, MASLD was introduced in 2023 to replace the previous nomenclature of non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD). This new term/definition introduced changes in the diagnostic criteria and underscores the direct link between cardio-metabolic risk and this prevalent liver disease. In this context, the present review examines the clinical and pathophysiological links between MASLD and cardiovascular disease (CVD), providing a robust evidence synthesis of primarily systematic review data on the association between MASLD and coronary artery disease (CAD), atrial fibrillation (AF), and heart failure (HF). This association appears to be not only synergistic, but also independent of other known CVD risk factors, highlighting MASLD as a key cardio-metabolic risk factor that merits prompt diagnosis and treatment. The development of MASLD-related cardiovascular morbidity increases with the severity of the underlying hepatic pathology, particularly with progression to steatohepatitis and fibrosis. Notably, growing evidence highlights the links between MASLD and CVD through cardiac structural, electrical, and functional alterations that can progress to CAD, AF, and new-onset HF. Recognizing these links in clinical practice underscores the importance of early detection and multi-disciplinary management of MASLD to prevent disease progression and CVD complications. Full article

Metabolic dysfunction–associated fatty liver disease (MAFLD) is now the leading indication for liver transplantation (LT), reshaping the landscape of transplant hepatology. Its close association with obesity, type 2 diabetes, cardiovascular disease, and extrahepatic malignancies poses unique challenges throughout the transplant continuum. This narrative review synthesizes current evidence across the pre-, peri-, and post-transplant spectrum, with a focus on practical implications for clinical management. We explore pre-transplant evaluation, focusing on how metabolic comorbidities, frailty, and organ allocation disparities intersect with emerging interventions such as GLP-1 receptor agonists, bariatric surgery, and structured weight loss programs. The increase in pediatric MAFLD, especially its early-onset aggressive form, indicates an evolving and concerning future burden on transplant programs. In the peri-operative and post-transplant periods, we address MAFLD recurrence, cardiometabolic complications, and the rising incidence of new cancers, particularly in relation to calcineurin inhibitor (CNI) exposure. Customized immunosuppression strategies, using mTOR inhibitors and mycophenolate mofetil, are discussed for their role in balancing graft protection with reducing cancer risk. We also review the application of machine perfusion technologies to optimize and expand the pool of steatotic donor livers. Future directions include the development of non-invasive diagnostic biomarkers, precision immunosuppression, and genomics-based risk stratification. Collectively, these insights emphasize the urgent need for multidisciplinary, patient-specific approaches and prospective, multicenter studies to optimize outcomes and equity in the era of MAFLD-driven liver transplantation. Full article

Background: Metabolically Associated Fatty Liver Disease (MAFLD) is a prevalent liver disorder closely tied to metabolic dysfunction, insulin resistance, and chronic low-grade inflammation. Vascular Endothelial Growth Factor (VEGF) may have a dual interesting role in MAFLD pathophysiology—supporting vascular repair in early stages, but potentially contributing to fibrosis in later stages. In this study, berberine (BBR), a plant-derived isoquinoline alkaloid, exhibits multiple beneficial properties, including anti-inflammatory, antioxidant, and endothelial-protective effects, on the study group, perhaps by influencing VEGF concentration. Objective: This study aimed to investigate the effectiveness of BBR in addressing vascular function parameters linked to MAFLD, particularly its impact on serum VEGF levels and arterial stiffness. Methods: This randomized, double-blind, placebo-controlled clinical trial enrolled seventy individuals with MAFLD who were overweight or obese. Participants were randomly assigned in a 1:1 ratio to receive either BBR (1500 mg/day) or a placebo orally for 12 weeks. The following parameters were assessed pre- and post-intervention: VEGF, brachial SBP (Systolic Blood Pressure)/DBP (Diastolic Blood Pressure), MAP (Mean Arterial Pressure), AIx (Augmentation Index), AP (Aortic Pressure), number of waveforms, Pulse Pressure (PP), PWV (Pulse Wave Velocity), and PWA-SP/PWA-DP (Pulse Wave Analysis Systolic/Diastolic Pressure). The results for the metabolic parameters—FLI (Fatty Liver Index)—and anthropometric parameters—BMI (Body Mass Index), fat mass corp—and laboratory parameters, among them, hsCRP (high-sensitivity C-reactive protein), were published by us earlier. Results: In the BBR-treated cohort, VEGF concentrations demonstrated a statistically significant increase following the intervention, rising from a baseline mean of 456.23 ± 307.61 pg/mL to 561.22 ± 389.77 pg/mL (p < 0.0001). In the BBR group, a significant reduction in PWA-SP was observed after 12 weeks of supplementation (134.85 ± 16.26 vs. 124.46 ± 13.47 mmHg, p < 0.0001). No statistically significant differences were observed in the parameters determining arterial stiffness in the BBR and placebo groups. In the BBR group, delta VEGF correlated negatively with delta FLI; no such associations were observed in the placebo group. Changes in PWV were consistent and significantly correlated with changes in brachial SBP/DBP, PWA-SP, PWA-DP, and MAP. No serious adverse events were reported, and BBR was well tolerated. Conclusions: BBR appears to be a safe and promising adjunct in MAFLD therapy, potentially exerting reparative effects through VEGF modulation and vascular support. Further research is warranted to confirm its long-term impact and elucidate underlying protective mechanisms. Full article

Fungal polysaccharides represent a structurally diverse group of bioactive compounds with increasing recognition for their hepatoprotective potential. This review synthesizes current evidence on their roles in the prevention and treatment of liver diseases, including alcohol-related liver disease (ALD), metabolic dysfunction-associated fatty liver disease (MAFLD), or toxin-induced injury. The analyzed studies demonstrate that polysaccharides isolated from species such as Lentinula edodes, Grifola frondosa, Ganoderma lucidum, Coriolus versicolor, and Cordyceps militaris exert beneficial effects by reducing oxidative stress, attenuating inflammation, and improving metabolic homeostasis. Mechanistically, these effects are mediated through the regulation of multiple signaling pathways, including Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Nuclear factor erythroid 2–related factor 2 (Nrf2), and NOD-like receptor protein 3 (NLRP3) inflammasome, as well as modulation of gut microbiota. Fungal polysaccharides were also shown to improve hepatic function by lowering serum biomarkers of liver injury and ameliorating histopathological damage. Presented evidence indicates that fungal polysaccharides possess considerable potential as multifunctional hepatoprotective agents, highlighting the need for further mechanistic insight and clinical validation. Full article

Background/Objectives: In the present study, the Metabolic dysfunction-associated fatty liver disease (MAFLD) and Metabolic dysfunction-associated steatotic liver disease (MASLD) diagnostic criteria were applied to evaluate the relative performance in predicting short-term advanced fibrosis (AF) progression (AFpr) and hepatocellular carcinoma (HCC), as well as an ancillary outcome, i.e., the occurrence of acute cardiovascular events (ACEs) in steatotic liver disease (SLD) patients. Methods: We retrospectively analyzed the data stored in the University Hospital (UH)’s Official Health Documents Digitization Archive of 931 SLD patients, with a follow-up of 3 years. Based on the Body Mass Index (BMI), patients were subdivided into lean “L” (BMI < 25 kg/m²) (n = 134) and not-lean “NL” (n = 797), and, subsequently, into NL-MASLD (n = 206), NL-MASLD/MAFLD (n = 481), NL-MAFLD (n = 110), L-MASLD (n = 39), L-MASLD/MAFLD (n = 68), and L-MAFLD (n = 27). All study outcomes (AFpr, HCC, and ACE) were primarily evaluated in NL-SLD and by conducting a sub-analysis of L-SLD individuals. Results: MASLD and MAFLD criteria similarly estimated [p = 0.076] the overall 3-year risk of AF progression in NL-SLD. In the L-SLD sub-analysis, MAFLD criteria better estimated the overall 3-year risk of AF progression [p = 0.006]. Multivariate competing risk analysis (adjusted for sex, age, diabetes, steatosis, and fibrosis severity) revealed diabetes [adjusted Hazard Ratio (aHR) = 2.113, p = 0.001], high-sensitivity C-reactive protein (aHR = 1.441; p = 0.02), and Homeostatic Model Assessment for Insulin Resistance (aHR = 1.228; p = 0.03) as being associated with AF progression in L-MAFLD. Compared to MAFLD, MASLD diagnostic criteria similarly estimated the 3-year risk of HCC occurrence both in NL [HR = 1.104, C.I. 95%: 0.824–1.593, p = 0.741] and L [HR = 1.260, C.I. 95%: 0.768–2.104, p = 0.701] patients. Finally, no significant differences were reported between the MAFLD or MASLD criteria for ACE risk occurrence in all study groups. Conclusions: The MAFLD criteria better estimate the AF progression risk, limited to L-SLD patients. Full article

Background and Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is increasingly prevalent and linked to liver and cardiometabolic complications. Although liver biopsy remains the diagnostic gold standard, its invasiveness limits routine use, and imaging modalities show variable accuracy. Non-invasive indices such as triglyceride-glucose (TyG), triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist circumference (TyG-WC), and the fatty liver index (FLI) are recommended for screening, yet their performance in Vietnam remains unclear. This study evaluated and compared these indices in Vietnamese adults. Methods: A cross-sectional study was conducted at the Health Screening Department, University Medical Center Ho Chi Minh City (September 2024–January 2025). After exclusions, 290 adults undergoing routine check-ups with abdominal ultrasound were included. Clinical and laboratory data were collected to calculate TyG, TyG-BMI, TyG-WC, and FLI, and their diagnostic performance for MAFLD was compared using logistic regression and receiver operating characteristic (ROC) analysis, with area under the ROC curve (AUROC) and 95% confidence intervals (CIs). Results: Of 290 participants, 32.76% were diagnosed with MAFLD. Patients with MAFLD were older, more frequently male, and had higher body mass index (BMI), waist circumference (WC), blood pressure (BP), metabolic comorbidities, and abnormal biochemical parameters compared with non-MAFLD. The highest diagnostic performance was observed with TyG-BMI and FLI, both showing area under the receiver operating characteristic curve (AUROC) = 0.89, followed by TyG-WC (0.88) and TyG (0.82). In gender-stratified analysis, indices performed better in females; TyG-BMI achieved the highest AUROC of 0.91, comparable to FLI (0.90). Conclusions: TyG, TyG-BMI, TyG-WC, and FLI demonstrated excellent and comparable diagnostic accuracy for MAFLD, with superior performance in women. These indices represent practical, non-invasive tools for MAFLD screening in both clinical and community settings. Full article

Emerging evidence highlights extracellular vesicles (EVs), especially exosomes, as critical molecular messengers linking pediatric obesity to multi-organ complications. This scoping review synthesizes current knowledge on EVs-mediated intercellular communication that exacerbates inflammation, insulin resistance, endothelial dysfunction and organ-specific damage. Data demonstrate that adipose- and endothelial-derived EVs carry bioactive cargo, microRNAs, proteins, and lipids, that modulate key pathways driving metabolic derangements and vascular injury, often preceding detectable clinical biomarkers. Notably, maternal obesity influences EVs composition in breast milk, shaping early-life metabolic programming and offspring risk of obesity. Recent studies underscore the diagnostic and therapeutic potential of EVs in obesity-related conditions such as metabolic-associated fatty liver disease (MAFLD), early renal injury, and cardiovascular dysfunction in children. Furthermore, EVs released in response to exercise or bariatric surgery may mediate systemic metabolic improvements, offering a novel window into personalized interventions. Despite promising findings, standardization of EV isolation and profiling in pediatric research is lacking, and large-scale longitudinal studies are urgently needed. By deepening our understanding of EVs biology, clinicians may advance early detection, risk stratification, and targeted therapies to interrupt the progression from childhood obesity to lifelong metabolic and cardiovascular disease. Full article

Background: Both lipid metabolism disorders and inflammation are critical contributors to the progression of metabolic-associated fatty liver disease (MAFLD), yet integrated analyses identifying key genes linking them remain scarce. Methods: Differentially expressed genes in MAFLD were extracted from the GSE135251 dataset and intersected with lipid metabolism- and inflammation-related genes from Molecular Signatures Database (MSigDB). Machine learning on GSE135251, followed by validation on GSE89632, identified key genes. Functional enrichment, immune microenvironment profiling, and nomogram analysis were subsequently conducted. Cellular heterogeneity was assessed using the single-cell sequencing (scRNA-seq) dataset GSE186328, and gene expression in MAFLD mice was validated via real-time Polymerase Chain Reaction (PCR). Activators targeting these genes were predicted using Drug Signatures Database (DsigDB). Results: Four genes—FADS1, FADS2, GLB1, and PNPLA3—were identified as key regulators involved in both lipid metabolism disorders and inflammation in MAFLD. These genes were co-enriched in ribosome-related pathways. GLB1 correlated strongly with CD56dim natural killer cells in immune infiltration analysis. A diagnostic nomogram integrating these genes demonstrated exceptional discriminatory power, with Area Under the Curve (AUC) values of 0.98981 for GSE135251 and 0.9204 for GSE89632. ScRNA-seq revealed elevated FADS1, FADS2, and GLB1 expression in MAFLD-associated NK/T cells compared to controls. Real-time PCR confirmed significant upregulation of all four genes in MAFLD mice. Drug prediction identified estradiol as a potential activator targeting these genes. Conclusions: This study identified FADS1, FADS2, GLB1, and PNPLA3 as key genes involved in the progression of MAFLD, linking metabolic dysfunction and inflammation. Full article

Irritable Bowel Syndrome (IBS) and Metabolic dysfunction-associated fatty liver disease (MAFLD) have traditionally been viewed as disorders of distinct organ systems. IBS is a gut–brain axis disorder characterized by abdominal pain, altered bowel habits, and psychological comorbidities. MAFLD, recently redefined to emphasize its metabolic underpinnings, is the hepatic manifestation of systemic metabolic dysfunction. Growing evidence suggests that these conditions share overlapping pathophysiological mechanisms linked through disruption of the gut–liver–brain axis (GLBA), including psychological stress, gut dysbiosis, impaired intestinal permeability, systemic inflammation, and altered neuroendocrine signaling. Neuroimaging studies further reveal functional alterations in brain regions responsible for interoception, emotional regulation, and stress responsiveness in both disorders. This narrative review explores how psychological distress influences the onset and progression of IBS and MAFLD via GLBA dysfunction and stress-induced epigenetic reprogramming. A targeted literature search of major biomedical databases, supplemented by manual screening, identified relevant observational, clinical, neuroimaging, and molecular studies. Findings indicate that chronic psychological distress activates the hypothalamic–pituitary–adrenal (HPA) axis, elevates cortisol, disrupts gut microbiota, and reduces vagal tone; amplifying intestinal permeability and microbial translocation. These changes promote hepatic inflammation and gastrointestinal symptoms. Stress-related epigenetic modifications further impair GLBA communication, while psychological and lifestyle interventions may reverse some of these molecular imprints. Recognizing the shared neuromodulation and epigenetic mechanisms that link IBS and MAFLD opens promising avenues for integrated therapeutic strategies targeting the GLBA to improve outcomes across both conditions. Full article

Background: Fetuin-A, a hepatokine implicated in metabolic regulation, has been associated with both metabolic syndrome and cardiovascular disease. However, its specific role in type 2 diabetes mellitus (T2DM) remains incompletely understood. Objective: This study aimed to investigate the relationship between fetuin-A levels and key components of metabolic syndrome (abdominal obesity, arterial hypertension, hyperglycemia, hypertriglyceridemia and low high-density lipoprotein cholesterol) as well as other cardiovascular risk markers, including metabolic dysfunction-associated fatty liver disease (MAFLD), carotid intima-media thickness (CIMT), and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Methods: A total of 51 patients with T2DM not receiving insulin therapy were enrolled. Participants underwent clinical, biochemical, and imaging evaluations. Hepatic steatosis was assessed via abdominal ultrasonography, and subclinical atherosclerosis was evaluated using CIMT measured with Doppler ultrasonography. Serum fetuin-A was quantified by ELISA. Results: Hepatic steatosis was significantly associated with metabolic syndrome, increased CIMT, and dyslipidemia (elevated total cholesterol, triglycerides, and reduced HDL cholesterol). Although no direct correlation was found between fetuin-A levels and hepatic steatosis, multivariate analysis revealed that fetuin-A concentrations were significantly influenced by total cholesterol and LDL cholesterol levels. Conclusions: Fetuin-A appears to be linked to lipid abnormalities in T2DM and may contribute to cardiovascular risk in this population. These findings support the potential utility of fetuin-A as a biomarker and possible therapeutic target for dyslipidemia management in diabetic patients. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) share overlapping pathophysiological mechanisms, including insulin resistance and chronic inflammation. Recent evidence suggests that Orosomucoid-2 (ORM2), an acute-phase immunomodulatory protein, may play a role in metabolic regulation; however, its specific involvement in MAFLD remains unclear. This study examined the association between circulating ORM2 levels and the severity of hepatic steatosis, insulin resistance, and T2DM in a cohort of 449 adults. MAFLD was assessed using FibroScan^® with hepatic steatosis categorized by Controlled Attenuation Parameter (CAP) scores, while plasma ORM2 levels were measured via ELISA. Statistical analyses using Spearman correlation and multiple logistic regression revealed that elevated ORM2 levels were significantly correlated with greater hepatic steatosis, insulin resistance, triglycerides, ALT, and hip circumference (p < 0.001). Individuals with severe steatosis (CAP > 290 dB/m) had markedly higher ORM2 levels (312.3 ng/mL) compared to those with normal CAP scores (210.4 ng/mL; p < 0.001). ORM2 was identified as an independent predictor of steatosis severity and after adjusting for several metabolic variables (AOR = 1.005; 95% CI: 1.002–1.007). ROC analysis incorporating ORM2 and metabolic variables demonstrated strong predictive capability for MAFLD (AUC = 0.864, 95% CI: 0.825–0.902). These findings support ORM2 as a promising non-invasive diagnosis for MAFLD, involving only blood sampling without direct invasion of the liver and associated metabolic dysfunction. Full article

Diseases such as obesity and metabolic-dysfunction-associated fatty liver disease (MAFLD) are often associated with changes in gut microbiota composition. The present study aims to investigate the relationship between the potential preventive effects of an Opuntia ficus-indica var. colorada cactus pulp extract on obesity and hepatic steatosis, and changes in gut microbiota composition, in a murine model fed a high-fat high-fructose diet. The low-dose extract was the most effective in reducing hepatic TG (−12.5%) and the weight of subcutaneous and visceral adipose tissue (−18.4% and 11.4%, respectively), while the high dose led to improved serum lipid profile (−74.2% in TG, −37.2% in total cholesterol, −50.5% in non-HDL cholesterol and +71.7% in HDL cholesterol). Opuntia extract supplementation did not prevent the dysbiosis in gut microbiota produced by the high-fat high-fructose diet. However, modifications in its composition, consistent with an increment in both Adlercreutzia muris and Cutibacterium acnes, and a reduction in Massiliimalia timonensis, were observed. It can be proposed that these changes may contribute to the extract effects against obesity and liver steatosis. Nevertheless, further research is required to establish a direct link between the anti-obesity and anti-steatotic effects and the functionality of the bacteria modified by the treatment. Full article

Background and Aims: Multiple genetic variants have been associated with disease prevalence and outcomes in middle-aged people with metabolic dysfunction-associated fatty liver disease (MAFLD). However, genetic studies in older adults have been lacking. We aimed to understand their clinical relevance in healthy older persons. Methods: A secondary analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized trial involving community-dwelling older adults ≥ 70 years without prior cardiovascular disease events or life-limiting illness at enrolment. The Fatty Liver Index (FLI) was used to identify MAFLD at baseline. We assessed the associations between six previously reported MAFLD-associated genetic variants with prevalent MAFLD at baseline, and the associations of these variants with cardiovascular disease events and all-cause mortality. Results: A total of 8756 participants with genetic data were stratified according to the FLI, with 3310 having MAFLD at baseline. The follow-up was for a median of 8.4 (IQR 7.3–9.5) years. Variants in two genes (GCKR and HSD17B13) were associated with prevalent MAFLD (p < 0.05); PNPLA3, TM6SF2, LYPLAL1, and MBOAT7 were not. PNPLA3, TM6SF2, HSD17B13, GCKR, and LYPLAL1 were not associated with major adverse cardiovascular events (MACEs) or mortality in the overall cohort or in participants with MAFLD during the follow-up (all p > 0.05). Within the MAFLD group, homozygosity for the rs641738 C > T variant in the MBOAT7 gene was associated with a reduced risk of MACEs (HR 0.68 [95% CI 0.48–0.97]), but not all-cause mortality (HR 1.14 [95% CI 0.89–1.47]). This protective association remained significant after adjusting for multiple key covariates (aHR 0.64 [95% CI 0.44–0.92]). The results were similar when using the metabolic dysfunction-associated steatotic liver disease definition rather than MAFLD. Conclusions: The rs641738 C > T variant in MBOAT7 may confer protection against MACEs in older adults with MAFLD, independent of other clinical risk factors. Further validation using external cohorts is needed. Full article

Metabolic dysfunction-associated fatty liver disease (MASLD) is a chronic, non-communicable spectrum of diseases characterized by lipid accumulation. It is often asymptomatic, and its prevalence varies by region, age, gender, and economic status. It is estimated that 25% of the world’s population currently suffer from MAFLD, and 20 million patients will die from MAFLD-related diseases. In the last 20 years, tea and anti-obesity research have indicated that regularly consuming tea decreases the risk of cardiovascular disease, stroke, obesity, diabetes, and metabolic syndrome (MeS). In this review, we aimed to present studies concerning the influence of matcha extracts and epigallocatechin-3 gallate (EGCG) supplements on metabolic functions in the context of MAFLD in human and animal studies. The published data show promise. In both human and animal studies, the beneficial effects on body weight, cholesterol levels, and liver metabolism and function were noted, even in short-period experiments. The safety levels for EGCG and green tea extract consumption are marked. More experiments are needed to confirm the results observed in animal studies and to show the mechanisms by which green tea exerts its effects. The preliminary data from research concerning microbiota or epigenetic changes observed after polyphenols and green tea consumption need to be expanded. To improve the efficiency and availability of green tea or supplement consumption as a treatment for MAFLD patients, more research with larger groups and longer study durations is needed. Full article