Search Results (2,413)

As the rates of type 2 diabetes and obesity have increased globally, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic steatotic fatty liver disease (NAFLD), has risen concomitantly worldwide. MASLD is now the most common etiology of chronic liver disease and is the leading indication for liver transplantation in the United States. Patients with MASLD have an increased risk of progression to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, hepatocellular carcinoma, extrahepatic malignancies, as well as liver- and cardiovascular-related mortality. Diet and lifestyle modifications with a goal of ≥10% total body weight loss—required to reverse steatosis, steatohepatitis, and fibrosis—are often challenging and ineffective. Although novel pharmacotherapies have recently been approved and others are in development, cost, adherence, and adverse effects remain potential limitations. Bariatric surgery, including Roux-en-Y gastric bypass and sleeve gastrectomy, is highly efficacious and a cost-effective treatment for obesity and associated medical problems. However, bariatric surgery may be associated with morbidity and mortality. Endoscopic bariatric and metabolic therapy (EBMT) has recently emerged as a promising treatment modality and offers an alternative to surgery. Primary EBMTs include intragastric balloon placement, aspiration therapy, endoscopic sleeve gastroplasty, duodenal mucosal resurfacing, duodenal–jejunal bypass liner, and primary obesity surgery endoluminal (POSE 2.0). Secondary EBMTs include transoral outlet reduction, argon plasma coagulation of the anastomosis, and revisional endoscopic sleeve procedure. We review the recent literature on primary EBMTs and secondary EBMTs for the treatment of obesity and MASLD, the pathophysiologic mechanisms, efficacy, safety, and patient outcomes in MASLD in this narrative review. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis in individuals with at least one cardiometabolic risk factor, most commonly type 2 diabetes mellitus (T2DM). People with non-alcoholic fatty liver disease, even without other metabolic factors, have a higher risk of T2DM. MASLD includes isolated liver steatosis, metabolic dysfunction-associated steatohepatitis, fibrosis, cirrhosis, and MASH-related hepatocellular carcinoma. MASLD patients are also at a higher risk of developing T2DM than the general population. International guidelines recommend a stepwise approach for identifying those at high risk of fibrotic progression, using the FIB-4 index for initial screening, followed by transient elastography. The link between MASLD and T2DM is notable due to shared pathophysiological mechanisms, some of which are reversible with treatment used in T2DM. Many new glucose-lowering drugs have also proven effective in improving anthropometric and metabolic parameters, as well as the stage of hepatic steatosis and fibrosis. Recent evidence suggests that GLP-1RAs and SGLT2is have beneficial effects in MASLD patients with T2DM. Specifically, GLP-1RAs improve hepatic insulin signaling, modulate lipid metabolism, reduce inflammation, and decrease hepatocyte oxidative stress. European guidelines recommend resmetirom as a MASH-targeted therapy, if locally approved, for adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥ 2) and GLP-1RAs in MASH, including compensated cirrhosis, but they should be used for their respective indications, such as T2DM and obesity. Given the post-COVID burden of MASLD and its high risk of liver fibrosis progression among T2DM patients, this review specifically provides an overview of the complex relationship between MASLD and T2DM. Additionally, it examines current understanding of liver fibrosis evaluation and the effects of novel treatment options, with a particular focus on glucose-lowering therapies and their effects on necroinflammation, hepatic fat accumulation, and fibrosis progression in patients with MASLD and T2DM. Full article

Objective: To develop a superoxide dismutase (SOD) fluorescent detection probe based on Phycoerythrin (PE) from Porphyridium cruentum for real-time monitoring of SOD activity, a core biomarker of oxidative stress, in a nonalcoholic fatty liver disease (NAFLD) model, and to explore the regulatory effect of astaxanthin. Methods: Phycoerythrin and SOD were covalently coupled using the heterobifunctional cross-linker N-Succinimidyl 3-(2-pyridyldithio) propionate (SPDP), and the probe concentration and incubation time were optimized. A NAFLD model was established in HepG2 cells induced by free fatty acids (FFAs). The fluorescence intensity of the probe was detected by flow cytometry, and the intervention effect of astaxanthin was evaluated by measuring triglyceride (TG)/total cholesterol (TC) contents and SOD activity. Results: The optimal conditions for the Phycoerythrin-SOD probe were determined. Astaxanthin at 20 μM significantly reduced FFA-induced TG (56.8%) and TC (63.6%) contents and restored SOD activity to 60% of that in the control group. Conclusion: The Phycoerythrin-SOD probe serves as an efficient tool for dynamic monitoring of SOD activity in NAFLD. Astaxanthin alleviates liver injury by multi-target regulation of lipid metabolism and antioxidant pathways. Full article

Black sesame pigment (BSP), a key macromolecular component of the traditional food–medicine black sesame, holds potential for improving non-alcoholic fatty liver disease (NAFLD), but its mechanisms remain unclear. We evaluated BSP and fired black sesame pigment (FBSP) in a high-fat diet/streptozotocin-induced NAFLD mouse model. An integrated multi-omics strategy—encompassing network pharmacology, urinary metabolomics, and 16S rRNA sequencing—was employed to identify potential targets and pathways. Key findings were subsequently validated in a human liver organoid model of NAFLD. FBSP treatment significantly alleviated hepatic steatosis and dysfunction in mice. Multi-omics analysis revealed that FBSP reshaped the gut microbiota (increasing Lactobacillus and Bacteroides) and influenced host glycolysis/gluconeogenesis metabolism. Both omics predictions converged on the HIF-1 signaling pathway. In human liver organoids, FBSP reduced lipid accumulation and inflammation, and modulated the expression of core HIF-1 pathway genes. This study demonstrates that FBSP ameliorates NAFLD, potentially through a gut–liver axis mechanism that involves microbiota remodeling and subsequent modulation of the hepatic HIF-1 signaling pathway. Our findings position FBSP as a promising food-derived candidate for NAFLD intervention. Full article

Sympathetic nervous system (SNS) imbalance is a common pathological basis for cardiovascular diseases, non-alcoholic fatty liver disease, and diabetes. This review focuses on these diseases, analyzing two core mechanisms: excessive sympathetic excitation induced by endoplasmic reticulum stress (ERS) or autophagy dysfunction in key central nuclei (e.g., hypothalamus, rostral ventrolateral medulla); and ERS/autophagy abnormalities in peripheral target organs caused by chronic SNS overactivation. Existing studies confirm that chronic SNS overactivation promotes peripheral metabolic overload via sustained catecholamine release, inducing persistent ERS and disrupting the protective unfolded protein response (UPR)–autophagy network, ultimately leading to cell apoptosis, inflammation, and fibrosis. Notably, central ERS or autophagy dysfunction further perturbs autonomic homeostasis, exacerbating sympathetic overexcitation. This review systematically elaborates on SNS overactivation as a critical bridge mediating UPR–autophagy network dysregulation in central and peripheral tissues, and explores therapeutic prospects of targeting key nodes (e.g., chemical chaperones, specific UPR modulators, nanomedicine), providing a theoretical basis for basic research and clinical translation. Full article

Introduction: Today, scientists are searching for alternative approaches to preventing metabolic diseases, particularly non-alcoholic fatty liver disease, which reduces the healthy life expectancy of the working population. Fungi, such as Hericium coralloides (Scop.) Pers., are promising raw materials for extracting bioactive substances with preventative potential. Materials and Methods: This review covered review and research articles published over the last 42 years and indexed in the databases of the eLIBRARY.RU, the National Center for Biotechnology Information, and Scopus. Results and Discussion: It has been established that H. coralloides is valued for its nutritional properties due to its rich protein, fat, and mineral composition. It is in demand for pharmaceutical purposes due to its content of bioactive metabolites. The most studied metabolites are lovastatin and ergothioneine. The activity of these biologically active substances against NAFLD has been confirmed by studies in vitro and in vivo. Market analysis revealed that most dietary supplements contain fungal mycelium or its extract. It is preferable to use pure metabolites of H. coralloides as nutrients in dietary supplements and functional foods, since it allows the scientists to standardize their doses, target the therapeutic effect (immunity, neuroprotection, or antitumor), and reduce the required intake of the product. Since this fungus is a rare species in nature, its biomass should be grown in vitro for industrial use. Conclusions: Further research will focus on developing methods for extracting H. coralloides metabolites and assessing their biopotential in vivo and clinical studies. Full article

Background/Objectives: This study evaluated whether yoghurt containing Apilactobacillus kunkeei DSM 12361 protects rats against non-alcoholic fatty liver disease (NAFLD). We hypothesized that this fructophilic probiotic, with anti-inflammatory properties, may affect NAFLD progression by improving the gut microbiome, lowering intestinal ethanol production, and modulating inflammatory and metabolic pathways linked to hepatic fat accumulation. Methods: Wister rats were randomized into three groups; rats in the control group (HFrD) were fed a high-fructose (70%) diet while rats in experimental groups were fed the same diet mixed with 10% of yoghurt containing YC-180 starter culture (HFrD-Y) or yoghurt containing YC-180 and Apilactobacillus kunkeei DSM 12361 (HFrD-Y-A). Results: After six weeks of intervention, levels of plasma triglycerides, cholesterol, glucose, liver enzymes (ALT and AST), interleukin (IL)-6, fecal ethanol, Enterobacteriaceae, and hepatic index were significantly increased (p < 0.05) in the HFrD group as compared to rats in both experimental groups. Moreover, plasma levels of liver enzymes, lipid profile, glucose, and IL-6 were significantly lower (p < 0.05) in rats of the HFrD-Y-A group than those in the HFrD-Y group. Furthermore, plasma levels of IL-10 and fecal Lactobacilli and Bifidobacteria were significantly increased (p < 0.05) in the experimental groups when compared to rats in the control group. Conclusions: In sum, the obtained results indicated that yoghurt containing Apilactobacillus kunkeei could decrease the risk of non-alcoholic fatty liver disease (NAFLD) through (a) blocking the inflammation process associated with NAFLD, (b) enhancing the lipid profile, (c) lowering fecal ethanol, and (III) decreasing the levels of fecal Enterobacteriaceae in comparison with levels of fecal Lactobacilli and Bifidobacteria in rats. More research on molecular mechanisms of the potential effects of the Apilactobacillus kunkeei strain against NAFLD is still required. Full article

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder associated with impaired lipid metabolism and oxidative stress. As a natural antioxidant and dithiol compound, α-lipoic acid (ALA) may play a beneficial role in modulating hepatic metabolism. This study investigates the potential mechanisms through which ALA may alleviate NAFLD. Methods: To construct an NAFLD model, NCTC 1469 cells were exposed to oleic acid and palmitic acid (OA/PA) and glucose for 24 h. RT-qPCR, Western blotting, and siRNA analyses were used to examine the effects and mechanisms of ALA. In vivo, C57BL/6J mice were fed a high-fat diet for 11 weeks and treated with ALA (200 mg/kg/day, intragastrical) for 4 weeks to evaluate its impact on NAFLD. Results: In NCTC 1469 cells exposed to OA/PA and glucose, ALA markedly reduced lipid accumulation by activating TFEB, which in turn promoted fatty acid β-oxidation and chaperone-mediated autophagy (CMA). Furthermore, ALA activated NRF2-dependent CMA and mitigated oxidative stress. Inhibition of AMPK or silencing of TFEB/NRF2 abolished these effects, indicating the key role of the AMPK–TFEB/NRF2 axis. In HFD-fed mice, ALA alleviated hepatic steatosis, serum lipid abnormalities, and liver injury, consistent with its activation of CMA and β-oxidation and reduction in oxidative stress via this pathway. Conclusions: ALA synchronously activates CMA, β-oxidation, and antioxidant responses via a unified AMPK pathway to reduce lipid accumulation and oxidative stress, providing a mechanistically integrated therapeutic strategy for NAFLD. Full article

Objectives: This study aims to explore the therapeutic effect and mechanism of stir-roasted deer velvet antler with ghee (ZLR) on Non-Alcoholic Fatty Liver Disease (NAFLD). Methods: This study used proteomics to analyze the protein composition of roasted deer antler velvet. It established a high-fat diet (HFD)-induced NAFLD rat model and evaluated the therapeutic effects of different dosage groups, including liver injury, oxidative stress, glucose metabolism, steatosis, and insulin homeostasis (via fasting glucose tolerance). Transcriptomics explored the mechanism. Gene expression and Western blot detected lipid metabolism-related gene expression. In vivo experiments validated that ZLR-containing serum alleviates NAFLD and reduces reactive oxygen species levels. Results: The results indicated that ZLR could significantly reduce the body weight, liver weight and degree of hepatic steatosis in HFD rats, improve glycolipid metabolism and insulin sensitivity, and alleviate oxidative stress damage. The mechanism involves activating the adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor (AMPK/PPAR) signaling pathway, regulating the expression of lipid metabolism-related genes, promoting fatty acid oxidation, and reducing fat deposition. The results of in vitro experiments show that ZLR-containing serum can effectively reduce lipid droplet production in liver cells and effectively alleviate oxidative stress damage in liver cells. Conclusions: The traditional Chinese medicine processed product ZLR can regulate lipid metabolism in the body and alleviate the degree of NAFLD by activating the AMPK and PPAR signaling pathways. It provides new ideas for the clinical treatment of NAFLD. Full article

Metabolic associated fatty liver disease (MAFLD), redefined from non-alcoholic fatty liver disease (NAFLD), is a global health concern driving the search for dietary interventions based on natural compounds. Phloroglucinaldehyde (PGA), a primary phenolic metabolite of the widely consumed anthocyanin cyanidin-3-glucoside (C3G) found in berries and other fruits, has emerged as a promising candidate due to its potential higher bioavailability than its parent compound. This study investigates the protective effects of PGA against high-fat diet (HFD)-induced MAFLD. Using both in vitro (LO2 cells) and in vivo (C57BL/6J mice) models, we found that PGA administration significantly attenuated body weight gain and hepatic steatosis, while reducing serum levels of TG, TC, liver transaminases (AST & ALT), and insulin resistance (p < 0.05). Further liver lipidomic profiling revealed that PGA supplementation specifically down-regulated 46 lipid species (p < 0.05), predominantly triglycerides characterized by long-chain and very-long-chain saturated fatty acids. Mechanistically, PGA enhanced the hepatic antioxidant capacity by increasing superoxide dismutase (SOD) activity (p < 0.05) and decreasing malondialdehyde (MDA) (p < 0.05) and exerted anti-inflammatory effects by reducing pro-inflammatory cytokines (IL-6, TNF, MCP-1) (p < 0.05) and endotoxin levels (p < 0.05). Correlation analyses further linked the down-regulated lipids to improvements in oxidative stress and inflammation. Our findings underscore that PGA, a key bioactive metabolite derived from dietary anthocyanins, alleviates MAFLD through its potent antioxidant and anti-inflammatory properties, highlighting its potential as a functional food ingredient or nutraceutical for metabolic health. Full article

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. This increases the demand for real-world evidence to complement findings from randomized controlled trials. The German IQVIA Disease Analyzer (DA) database, which is populated with anonymized electronic medical records from general practitioners and specialists, has become an increasingly valuable source for cardiovascular research. Over the past two decades, and especially between 2020 and 2025, numerous epidemiological studies have used this database to explore associations between cardiovascular risk factors, comorbidities, therapeutic patterns, and cardiovascular outcomes in large, broadly representative outpatient populations. This review synthesizes evidence from 13 selected DA-based studies examining atrial fibrillation, heart failure, cardiometabolic disease, lipid management, non-alcoholic fatty liver disease (NAFLD)–related cardiovascular risks, cerebrovascular complications, COVID-19-associated vascular events, and modifiable behavioral and anthropometric factors. These studies were selected based on predefined criteria including cardiovascular relevance, methodological rigor, large sample size, and representativeness of key disease domains across the 2000–2025 period. Eligible studies were identified through targeted searches of peer-reviewed literature using the German IQVIA Disease Analyzer database and were selected to reflect major cardiovascular disease domains, risk factors, and therapeutic areas. Across disease domains, the reviewed studies consistently demonstrate the DA database’s capacity to identify reproducible associations between cardiometabolic risk factors, comorbidities, and cardiovascular outcomes in routine outpatient care. While causal inference is not possible, the database enables the identification of clinically meaningful associations that inform hypothesis generation, help quantify disease burden, and highlight gaps in prevention or treatment. The database’s strengths include large sample sizes (often exceeding 100,000 patients), long follow-up periods, and high external validity, while limitations relate to coding accuracy, residual confounding, and the absence of detailed clinical measures. Collectively, the evidence underscores the importance of the DA database as a crucial platform for real-world cardiovascular research. Full article

The hepatic lymphatic system, long underappreciated, plays a critical role in liver physiology by maintaining interstitial fluid balance, removing metabolic waste, and facilitating immune surveillance. Emerging evidence indicates that lymphatic dysfunction contributes to the pathogenesis and progression of multiple liver diseases, including non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH), hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. This review summarizes current knowledge on hepatic lymphatic anatomy, physiology, and molecular regulation, highlights pathological alterations, and discusses potential therapeutic implications. A better understanding of the hepatic lymphatic system may enable the development of novel lymphatic-targeted strategies to improve liver health and treat liver disease. Full article

Non-alcoholic fatty liver disease (NAFLD) is a silent condition that can lead to fatal cirrhosis, with dietary factors playing a central role. The effect of various dietary interventions on male Wistar rats were evaluated in four diets: control, arsenic, sucrose, and arsenic–sucrose. SHG microscopy images from the right ventral lobe of the liver tissue were analyzed with a neural network trained to detect the presence or absence of collagen fibers, followed by the assessment of their orientation and angular distribution. Machine learning classification of SHG microscopy images revealed a marked increase in fibrosis risk with dietary interventions: <10% in controls, 24% with arsenic, 40% with sucrose, and 62% with combined arsenic–sucrose intake. Angular width distribution of collagen fibers narrowed dramatically across groups: 26° (control), 24° (arsenic), 15.7° (sucrose), and 2.8° (arsenic–sucrose). This analysis revealed four key statistical features for classifying the images according to the presence or absence of collagen fibers: (1) the percentage of pixels whose intensity is above the 15% noise threshold, (2) the Mean-to-Standard Deviation ratio (Mean/std), (3) the mode, and (4) the total intensity (sum). These results demonstrate that a diet rich in sucrose, particularly in combination with arsenic, constitutes a significant risk factor for liver collagen fiber remodeling. Full article

Background: Childhood obesity represents the most common nutritional and metabolic disorder in industrialized countries and constitutes a major public health concern. In Italy, 20–25% of school-aged children are overweight and 10–14% are obese, with marked regional variability. Excess adiposity in childhood is frequently associated with hypertension, dyslipidemia, insulin resistance, and non-alcoholic fatty liver disease (NAFLD), predisposing to future cardiovascular disease (CVD). Objective: To investigate anthropometric indicators of cardiometabolic risk in 810 children and adolescents aged 7–17 years who underwent assessment for competitive sports eligibility at the Sports Medicine Unit of Modena, evaluate baseline knowledge of cardiovascular health aligned with ESC, AAP (2023), and EASO guidelines. Methods: 810 children and adolescents aged 7–17 years undergoing competitive sports eligibility assessment at the Sports Medicine Unit of Modena underwent evaluation of BMI percentile, waist circumference (WC), waist-to-height ratio (WHtR), and blood pressure. Cardiovascular knowledge and lifestyle habits were assessed via a previously used questionnaire. Anthropometric parameters, blood pressure (BP), and lifestyle-related knowledge and behaviors were assessed using standardized procedures. Overweight and obesity were defined according to WHO BMI-for-age percentiles. Elevated BP was classified based on the 2017 American Academy of Pediatrics age-, sex-, and height-specific percentiles. Statistical analyses included descriptive statistics, group comparisons, chi-square tests with effect size estimation, correlation analyses, and multivariable logistic regression models. Results: Overall, 22% of participants were overweight and 14% obese. WHtR > 0.5 was observed in 28% of the sample and was more frequent among overweight/obese children (p < 0.001). Elevated BP was detected in 12% of participants with available measurements (n = 769) and was significantly associated with excess adiposity (χ² = 7.21, p < 0.01; Cramér’s V = 0.27). In multivariable logistic regression analyses adjusted for age and sex, WHtR > 0.5 (OR 2.14, 95% CI 1.32–3.47, p = 0.002) and higher sedentary time (OR 1.41 per additional daily hour, 95% CI 1.10–1.82, p = 0.006) were independently associated with elevated BP, whereas BMI percentile lost significance when WHtR was included in the model. Lifestyle knowledge scores were significantly lower among overweight and obese participants compared with normal-weight peers (p < 0.01). Conclusions: WHtR is a sensitive early marker of cardiometabolic risk, often identifying at-risk children missed by BMI alone. Baseline cardiovascular knowledge was suboptimal. The observed gaps in cardiovascular knowledge underscore the importance of integrating anthropometric screening with structured educational interventions to promote healthy lifestyles and long-term cardiovascular prevention. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is now recognized as the leading cause of chronic liver disease worldwide. MASLD spans a spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and is linked to progressive fibrosis and ultimately hepatocellular carcinoma (HCC). Growing evidence implicates cellular senescence (CS) and lipid droplets (LDs) as key drivers of disease progression, although their interaction remains poorly characterized. This review provides an integrative and stage-dependent synthesis of current mechanistic insights into how bidirectional crosstalk between CS and LD regulation shapes the transition from steatosis to MASH. Senescent hepatocytes display altered lipid metabolism, including upregulation of receptors such as cluster of differentiation (CD) 36, enhancing lipid uptake to meet increased energy demands. Initially, elevated free fatty acid influx can activate peroxisome-proliferator-activated receptor alpha (PPARα), promoting fatty acid oxidation (FAO) as a compensatory response. Over time, persistent CS under steatotic conditions leads to mitochondrial dysfunction and suppression of fatty acid oxidation (FAO), while the senescence-associated secretory phenotype (SASP), largely driven by nuclear factor—kappa B (NF-κB) signaling, promotes chronic hepatic inflammation. By framing LDs as active modulators of senescence-associated signaling rather than passive lipid stores, this review highlights how disruption of senescence–lipid feedback loops may represent a disease-modifying opportunity in MASLD progression. Full article