Search Results (598)

Non-alcoholic fatty liver disease (NAFLD), now increasingly termed metabolic dysfunction-associated steatotic liver disease (MASLD), is a growing cause of chronic liver disease with limited treatment options. Glucagon-like peptide-1 (GLP-1) receptor agonists, approved for type 2 diabetes and obesity, possess metabolic effects that may render them suitable for treating NAFLD and metabolic dysfunction-associated steatohepatitis (MASH). To evaluate the therapeutic effects of GLP-1 receptor agonists in adults with NAFLD, non-alcoholic steatohepatitis (NASH), MASLD, or MASH. PubMed, Scopus, Embase, and the Cochrane Library were systematically searched using keywords related to NAFLD and GLP-1 receptor agonists. Given heterogeneity in populations, designs, and outcomes, findings were synthesized narratively. The review is registered with PROSPERO (CRD420261337353). Twelve studies met the inclusion criteria. The most consistent outcome was a reduction in hepatic fat, seen with semaglutide, liraglutide, dulaglutide, and beinaglutide. Improvements in liver enzymes, particularly alanine aminotransferase, were less consistent and best regarded as supportive rather than definitive evidence of histological improvement. Histological benefits were strongest for steatohepatitis resolution in non-cirrhotic MASH. Fibrosis findings were mixed, with the greatest benefit in F2–F3 MASH and limited improvement in established cirrhosis. GLP-1 receptor agonists were generally well tolerated, with gastrointestinal symptoms the most common adverse effects. GLP-1 receptor agonists show promising liver-related benefits in NAFLD and MASH, particularly in obesity, type 2 diabetes, or earlier-stage disease. Their effects on advanced fibrosis and long-term outcomes remain uncertain, warranting larger, longer-term studies. Full article

Metabolic dysfunction–associated steatotic liver disease (MASLD) is now the most common chronic liver disorder worldwide. Once started with hepatic steatosis, it can progress to metabolic dysfunction–associated steaohepatitis (MASH), cirrhosis, and even hepatocellular carcinoma. Insulin resistance is a major driver of hepatic lipogenesis in this disease context. Gut barrier dysfunction also contributes to the progression to MASH by allowing bacterial lipopolysaccharide (LPS) to breach into the hepatic tissues. Amphibian skin secretion peptides (ASSPs) are therefore of particular interest, given their combined metabolic and antimicrobial activities. Some ASSPs enhance glucose-stimulated insulin secretion and GLP-1 release, whereas others attenuate LPS-driven inflammatory signaling. This review introduces these ASSPs with a focus on their insulinotropic/incretinotropic and immunomodulatory activities. Also, in the latter part, pharmaceutical strategies to improve blood circulation time and structural stability would be discussed. Full article

Mashed potatoes (MP) are widely consumed starch-based foods. However, their shelf life is limited by starch retrogradation during low-temperature storage, which causes texture hardening, water exudation, and sensory deterioration. Although natural polysaccharides can modulate starch properties, the specific anti-retrogradation effect of soluble arabinoxylan (AX) in complex MP matrices remains unknown. In this study, the effects of AX on the physicochemical and sensory qualities of MP during 7 d of storage at 4 °C were comprehensively investigated. Results demonstrated that AX significantly reduced the rheological moduli (i.e., G′ and G″ values) and hardness of stored MP. Additionally, LF-NMR, XRD, FTIR and SEM analyses, together with water holding capacity (WHC) measurement, revealed that AX improved water retention and restricted water mobility of the system, delayed starch recrystallization, inhibited the formation of short-range ordered structures, and physically disrupted the starch microstructure, thereby attenuating the overall starch retrogradation process. Moreover, the addition of AX helped maintain the sensory appeal of the products. These findings suggest that AX modulates the structural evolution of the starch matrix during storage. This distinguishes the present work from conventional hydrocolloid studies by demonstrating that AX can simultaneously inhibit starch retrogradation, stabilize color, and maintain soft texture. This work highlights the potential of AX as a clean-label multifunctional modifier to extend the shelf life of starchy convenience foods. Full article

The gut microbiota is increasingly examined as a therapeutic target because it contributes to epithelial barrier integrity, microbial metabolite production, bile acid transformation, immune regulation, and communication between the gut and distant organs. This structured narrative review synthesizes evidence on microbiota involvement in metabolic, gastrointestinal, hepatic, cancer, and neuroimmune conditions, including MASLD/MASH, inflammatory bowel disease, irritable bowel syndrome, obesity, type 2 diabetes, hypertension, colorectal cancer, Parkinson’s disease, and autism spectrum disorder. Across these conditions, microbiome findings are biologically plausible but heterogeneous. Many associations are shaped by diet, geography, medication exposure, host genetics, disease stage, sampling methods, and analytical pipelines. Microbial alterations should therefore be interpreted as context-dependent signals and candidate modifiers rather than universal causal markers. Conventional microbiota targeted strategies include diet, physical activity, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. These approaches are clinically familiar, but their effects are often broad, host specific, strain dependent, and difficult to assign to one mechanism. Fecal microbiota transplantation has the clearest clinical role in recurrent Clostridioides difficile infection, while evidence for most other indications remains inconsistent. Engineered microbial therapeutics offer greater experimental precision through signal sensing, payload delivery, metabolic modulation, and genetic circuit design. However, most evidence remains preclinical or early translational. Progress requires stronger human trials, standardized methods, mechanistic validation, safety monitoring, ecological containment, transparent reporting, and proportionate regulation. Full article

Background: Clostridioides difficile infection (CDI) remains a leading cause of hospital-acquired infection. Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and has been associated with increased infectious susceptibility. However, whether non-cirrhotic MASLD independently worsens inpatient CDI outcomes and whether this differs across the MASLD spectrum remain unclear. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) 2017–2023, identifying adult hospitalizations with a principal diagnosis of CDI. Patients with cirrhosis and alcoholic liver disease were excluded. Propensity score matching (1:1) was performed for the primary MASLD vs. non-MASLD comparison in the principal-diagnosis CDI cohort. To evaluate whether outcomes differ across the MASLD spectrum, survey-weighted multivariable logistic regression was used to compare K76.0-coded (MASLD without steatohepatitis) and K75.81-coded (MASH) hospitalizations against non-MASLD/MASH hospitalizations within the principal-diagnosis CDI cohort. The primary outcome was in-hospital mortality; secondary outcomes included complications, healthcare utilization, and discharge disposition. Results: The principal-diagnosis CDI cohort comprised 76,103 discharges (weighted ~380,515). MASLD prevalence among non-cirrhotic CDI hospitalizations nearly doubled from 1.98% in 2017 to 3.74% in 2023 (OR per year 1.089; p < 0.001). After propensity score matching (1756 pairs), MASLD was not associated with significantly higher in-hospital mortality (OR 1.252; p = 0.574) or most adverse outcomes, but was associated with lower odds of non-routine discharge (OR 0.794; p = 0.003). In the matched utilization analysis, length of stay and total charges were not significantly different, although the adjusted pre-match analysis showed higher charges among MASLD hospitalizations (+$4431; p = 0.001). Within the same principal-diagnosis cohort, K76.0-coded MASLD (n = 1988) was associated with lower odds of acute kidney injury (aOR 0.821; p = 0.004) and non-routine discharge (aOR 0.805; p = 0.001). K75.81-coded MASH (n = 197) was independently associated with higher in-hospital mortality (aOR 2.840, 95% CI 1.154–6.985; p = 0.023) and peritonitis (aOR 4.136, 95% CI 1.543–11.082; p = 0.005), although confidence intervals were wide and the number of MASH-coded hospitalizations was modest. Conclusions: The prevalence of MASLD among CDI hospitalizations is rising. Non-cirrhotic MASLD without steatohepatitis does not independently worsen inpatient CDI outcomes after adjustment, whereas K75.81-coded MASH may identify a higher-risk subgroup with increased mortality and peritonitis, pending confirmation in larger cohorts. These findings suggest that hepatic inflammatory activity, rather than steatosis alone, may drive adverse CDI outcomes and support further investigation of MASLD phenotyping in CDI risk stratification. Full article

Beer is one of the oldest and most widely consumed fermented beverages in the world. However, barley production is increasingly vulnerable to agricultural and socioeconomic pressures, particularly in temperate growing regions where rising temperatures threaten yield stability. In contrast, rice is projected to experience comparatively smaller yield declines, highlighting its potential as a more climate-resilient starch source for brewing. This opportunity is especially relevant in the United States, where Arkansas produces approximately half of the nation’s rice supply. Large commercial breweries have successfully incorporated rice through the use of cereal cookers, but these systems are often impractical for smaller operations because of their cost and space requirements. In addition, rice supplied to the brewing industry is often sourced as a byproduct of the edible rice market, where multiple cultivars may be blended, reducing consistency and obscuring cultivar-specific effects that influence brewing performance. This manuscript reviews variation among rice cultivars in the physical, chemical, and agronomic properties relevant to brewing and examines how these differences affect extract yield and processability. Particular emphasis is placed on practical strategies to overcome technical barriers, including alternative mashing approaches and the use of heat-stable exogenous enzymes to facilitate the use of milled rice without dedicated cereal-cooking infrastructure. Full article

Background/Objectives: Metabolic-dysfunction-associated steatotic liver disease (MASLD) and its progressive inflammatory/fibrotic form, metabolic-dysfunction-associated steatohepatitis (MASH), represent a growing global health burden. This progression is driven by complex mechanisms involving metabolic dysregulation, chronic inflammation, oxidative stress, and progressive fibrosis. To date, effective pharmacological therapies remain limited. Pentacyclic triterpenes have attracted increasing attention due to their broad biological activities and ability to modulate multiple molecular pathways implicated in chronic liver disease. This review aims to provide a mechanistic overview of the potential role of pentacyclic triterpenes in MASLD and MASH. Methods: A literature review was conducted using major scientific databases (PubMed and Web of Science) to identify experimental studies investigating pentacyclic triterpenes in metabolic liver diseases. Selected studies were analyzed according to triterpene structural classification, reported bioactivities, molecular targets, and experimental evidence from in vitro and in vivo models of MASLD/MASH or related pathogenic processes. Results: Pentacyclic triterpenes, especially ursolic acid, oleanolic acid, and glycyrrhizin, exhibit hepatoprotective effects including regulation of lipid metabolism, attenuation of oxidative and endoplasmic reticulum stress, suppression of pro-inflammatory signaling, inhibition of inflammasome activation, and reduction in hepatic stellate cell activation and extracellular matrix deposition. These effects involve modulation of signaling pathways, including AMPK, NF-κB, NLRP3, TGF-β, FXR, and MAPK. Preclinical evidence demonstrates improvements in steatosis, inflammation, and fibrosis in experimental models. Conclusions: Pentacyclic triterpenes emerge as multitarget modulators of MASH pathophysiology. However, translating preclinical evidence into well-designed clinical trials is necessary to validate their safety and efficacy in humans. Full article

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a global health priority affecting approximately 30% of the population. It represents the hepatic manifestation of metabolic syndrome, potentially progressing from simple steatosis to Metabolic Dysfunction-Associated Steatohepatitis (MASH), cirrhosis, and hepatocellular carcinoma. This review aims to compare current knowledge of MASLD in mouse models and humans, focusing on pathophysiology, histological phenotypes, and the role of preclinical imaging as a non-invasive translational screening tool. Methods: A literature search was conducted in PubMed and Web of Science to identify English-language publications from January 2020 to March 2026 on murine models and imaging techniques for MASLD, using pertinent keywords. Attention was given to highlighting similarities and differences between human and murine approaches. Results: MASLD arises from complex interactions between genetics, sedentary lifestyles, and imbalanced diets. While mouse models have been refined to capture the multifactorial interplay driving disease progression and are still essential for drug development, no single model fully mirrors the human condition. Histological assessment remains an essential tool for MASLD staging, in both humans and mouse models. However, imaging is increasingly emerging as an important complementary technique to non-invasively investigate MASLD. Conclusions: Mouse models are essential to address specific mechanistic and therapeutic questions, but understanding of their limitations and strengths is crucial for translational research. Integrating phenotype-driven approaches in both humans and mice, combining traditional histology, quantitative imaging, and metabolic profiling, as well as longitudinal, combined, and humanized preclinical models, will enhance translational alignment and accelerate the development of therapies for MASLD. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent liver-centred manifestation of systemic metabolic dysfunction. The gut–liver axis provides a biologically credible therapeutic rationale because intestinal dysbiosis, impaired barrier integrity, microbial metabolites, bile acid signalling, short-chain fatty acids, and trimethylamine N-oxide may influence hepatic steatosis, inflammation, and fibrogenesis. This narrative review critically evaluates dietary patterns, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT) as microbiome-directed strategies in MASLD. The comparative framework prioritises disease-specific human evidence, clinically meaningful endpoints, trial duration and sample size, reproducibility, safety, and feasibility. Dietary optimisation remains the most clinically grounded intervention, whereas probiotics and synbiotics show modest and heterogeneous signals on biochemical or metabolic surrogate endpoints. Prebiotics are mechanistically coherent but supported by limited liver-centred trials. Postbiotics and microbiome-mediated bioactives remain early-stage and require stricter definitional boundaries. FMT is investigational and should not be extrapolated from its established role in recurrent Clostridioides difficile infection. Most available evidence across all intervention categories relies principally on surrogate endpoints—including aminotransferases, insulin resistance indices, lipid parameters, and microbiome compositional shifts—rather than on validated liver-centred outcomes such as histological improvement or quantitative liver fat assessment; this constrains the strength of conclusions that can currently be drawn. Across all categories, microbiome modulation does not by itself establish liver disease modification, and no microbiome-targeted nutritional intervention has yet demonstrated histological benefit in MASLD. Future trials in this field should prioritise validated hepatic endpoints, phenotype-stratified patient enrolment, adequate follow-up duration, and direct comparisons between intervention categories to determine which microbiome-directed strategies, if any, deliver measurable and reproducible hepatic benefit beyond surrogate markers. Full article

Background: Given aspirin’s biologic plausibility for antifibrotic and antineoplastic effects, we conducted a systematic review and meta-analysis to examine the association between aspirin use and major liver-related outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD). To our knowledge, this is the first systematic review and meta-analysis restricted exclusively to patients with biopsy- or registry-confirmed MASLD. Methods: A comprehensive search of Ovid MEDLINE, Ovid EMBASE, Scopus, and Web of Science was performed in October 2025. Studies enrolling adults with a confirmed MASLD diagnosis were included; those with viral hepatitis or alcohol-related liver disease were excluded. Outcomes assessed included hepatocellular carcinoma (HCC), fibrosis progression, cirrhosis, all-cause and liver-related mortality, gastrointestinal (GI) bleeding, hemorrhagic stroke, and liver disease progression. Hazard ratios (HRs) with 95% CIs were pooled using random-effects models. Heterogeneity was assessed using I² statistics. Results: Seven studies met the eligibility criteria, with approximately 720,000 individuals included. Pooled analysis showed that aspirin use was associated with a significantly lower HCC risk (HR 0.59; 95% CI 0.43–0.81; I² = 83%). No statistically significant association was found between aspirin use and cirrhosis incidence (HR 0.55; 95% CI 0.13–2.37; I² = 83.4%) or GI bleeding (HR 1.11; 95% CI 0.74–1.66; I² = 98.9%). Among the two studies that explored all-cause mortality, aspirin was associated with a modest but statistically significant reduction in all-cause mortality (HR 0.86; 95% CI 0.78–0.95; I² = 0%). Conclusions: Aspirin use is associated with a reduced risk of HCC and all-cause mortality in MASLD without significantly increasing GI bleeding or hemorrhagic strokes. These associations may reflect aspirin’s anti-inflammatory properties in liver disease. Further RCTs are needed to verify the causal role of aspirin in MASLD management. Full article

The global burden of type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise at an alarming pace, with substantial pathophysiological overlap driven by insulin resistance, visceral obesity, and chronic low-grade inflammation. MASLD may progress to metabolic dysfunction-associated steatohepatitis (MASH), with increased risk of cirrhosis and hepatocellular carcinoma. Glucagon-like peptide 1 (GLP-1)-based therapies have transformed the management of T2DM and obesity. They exert pleiotropic effects whose basis remains incompletely understood. Concurrently, Akkermansia muciniphila has emerged as a keystone gut microbiota species with demonstrated hepatoprotective potential in preclinical models of MASLD/MASH. This narrative review positions A. muciniphila simultaneously as a target of GLP-1-mediated microbiome remodeling and as an independent modulator of hepatoprotection in MASLD/MASH. A structured search of PubMed, Scopus, and Web of Science (last searched: 12 April 2026) was conducted using terms related to Akkermansia muciniphila, GLP-1 receptor agonists, MASLD/MASH and T2DM. A total of 174 records were identified. Of these, 148 were excluded due to duplication or non-relevant study design. 26 studies (23 preclinical, 3 clinical) were included in the synthesis, directly addressing A. muciniphila. Preclinical evidence demonstrates that liraglutide, semaglutide, exenatide, and tirzepatide increase A. muciniphila abundance, while A. muciniphila in turn enhances endogenous GLP-1 secretion via the P9/ICAM-2 axis, forming a hypothetical positive feedback loop. A working mechanistic model integrating these bidirectional interactions is proposed, alongside a discussion of current limitations and future research priorities, including microbiome-guided clinical trials in MASLD/MASH populations. Full article

Circulating sex hormone-binding globulin (SHBG) concentrations are lower in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), reflecting its potential role in metabolic liver dysfunction. Our prior studies demonstrated that SHBG can attenuate MASLD by limiting hepatic lipid deposition, partly through suppression of lipogenic pathways, in both cellular and animal models. In the present work, we have examined whether SHBG could protect against development of liver fibrosis. For this purpose, in vitro and in vivo studies were performed. In vitro, we used co-cultures of human hepatocellular carcinoma cell line (HepG2) and human hepatic stellate cell line (LX-2) cells transfected using an SHBG expression vector vs. vehicle and treated with transforming growth factor beta 1 (TGF-β1). For in vivo studies we used wild-type and human SHBG transgenic mice developing liver fibrosis induced by carbon tetrachloride (CCl₄). Our results clearly showed that SHBG overexpression reduced the TGF-β1-induced expression in collagen in LX-2 cells. Moreover, SHBG overexpression reduced the CCl₄ induced liver fibrosis in both male and female mice. Histological examination revealed that SHBG transgenic mice had reduced NAS score and decreased collagen accumulation, assessed by Sirious Red staining. In addition, human SHBG transgenic mice treated with CCl₄ exhibited lower collagen 1A1 (Col1A1) protein levels when compared with wild-type CCl₄ treated mice. Mechanistically, SHBG attenuated fibrosis primarily through modulation of the TGF-β1/matrix metalloproteinases (MMPs)/tissue inhibitor metalloproteinases 1 (TIMP1) axis, characterized by reduced TGF-β1 levels, increased metalloprotease activity, and decreased TIMP1 levels compared with wild-type CCl₄ treated mice. Notably, female SHBG transgenic mice exhibited greater protection against fibrosis than males, indicating a sex-dependent effect likely mediated by differences in sex steroid signaling. Taken together, we demonstrate for the first time that SHBG protects against liver fibrosis by promoting collagen degradation via the TGF-β1/MMPs/TIMP1 pathway. Further research is needed to elucidate the role of sex steroids in the regulation of MMPs and the observed sexual dimorphism. Full article

Pharmacological treatment of metabolic-dysfunction-associated steatohepatitis remains challenging due to its complex pathophysiology. The endocannabinoidome (eCB) has emerged as a promising therapeutic target given its central role in energy homeostasis and its pharmacological tractability. Western-style diets high in fat and sugar exacerbate metabolic liver disease, highlighting the need for effective interventions. Here, we investigated the therapeutic potential of cannabinoid combinations targeting the eCB–liver axis in a Western diet-induced model of metabolic dysfunction. Two weeks of treatment reduced body weight, improved glycaemic control, and ameliorated liver pathology. These effects were accompanied by decreased liver weight, improved liver enzyme profiles, and reduced histological features of steatosis and injury. Overall, these findings suggest that modulation of the eCB system can induce acute improvements in metabolic and hepatic parameters under conditions of diet-induced metabolic stress. These results support further investigation into the eCB system as a therapeutic target, particularly to elucidate underlying mechanisms and longer-term effects. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now recognized as the principal hepatic manifestation of obesity and metabolic dysfunction. Its pathogenesis is complex and multifactorial, driven by insulin resistance, low-grade chronic inflammation, oxidative stress, gut microbiota alterations, and abnormalities in lipid metabolism; together, these promote steatosis, lipotoxicity, and progression to fibrosis which can lead to compensated advanced chronic liver disease (cACLD). MASLD is also a multisystem condition closely associated with an increased risk of major adverse cardiovascular events such as myocardial infarction, ischemic stroke, atrial fibrillation, and other extrahepatic complications. In this context, emerging metabolic therapies show significant potential for modifying the natural history of the disease. Glucagon-like peptide (GLP)-1 receptor agonists induce substantial weight loss and improve steatosis and necro-inflammatory activity. Sodium–glucose cotransporter 2 inhibitors (SGLT-2I) reduce glucotoxicity, promote modest weight loss, and lower hepatic fat content by improving insulin sensitivity and inflammatory signaling. Even more promising are dual GLP-1/GIP receptor agonists, which have demonstrated superior efficacy in metabolic control, reducing hepatic steatosis, and potentially modulating fibrotic processes, although definitive histological confirmation is still lacking. Overall, in this review, we discuss the physiopathological mechanisms of MASLD leading to cACLD along with the emerging therapies, such GLP1 receptor agonists, SGLT-2I, and GLP1/GIP which, when combined with structured lifestyle interventions, may attenuate progression toward steatohepatitis (MASH), fibrosis, and, thus, cirrhosis. Full article

Background/Objectives: Metabolic dysfunction-associated fatty liver disease (MAFLD), previously known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent chronic liver disease worldwide, affecting approximately 25% of the global population. MAFLD represents a broad disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The availability of experimental models that faithfully reproduce human metabolic and hepatic pathology is essential for elucidating disease mechanisms and advancing therapeutic development. This review aims to critically evaluate commonly used rodent models of MAFLD and provide guidance for model selection based on specific research objectives. Methods: A narrative, semi-systematic literature search was performed using PubMed Central, Ovid MEDLINE, and Google Scholar. Rodent models were classified according to their mode of disease induction, including diet-induced, genetically engineered, chemically or pharmacologically induced, and combination models. Models were assessed based on frequency of use, relevance to different stages of MAFLD progression, metabolic fidelity, and suitability for mechanistic studies and preclinical therapeutic evaluation. Results: Diet-induced models incorporating high fat, fructose, and cholesterol most closely recapitulate human metabolic dysfunction and are highly relevant for translational research and drug screening. Nutrient-deficient diets induce rapid steatohepatitis and fibrosis but lack key features of metabolic syndrome. Genetic models enable the targeted interrogation of specific metabolic and inflammatory pathways, whereas chemical and combination models accelerate fibrosis and HCC development. No single rodent model fully reproduces the entire spectrum of human MAFLD. Conclusions: Rodent models remain indispensable tools for MAFLD research; however, their applicability depends on alignment with the defined experimental goals. Careful selection of models based on disease stage, dominant pathogenic mechanisms, and translational intent is essential for improving reproducibility and clinical relevance. This review provides a practical framework to guide investigators in choosing appropriate preclinical models for mechanistic studies and therapeutic development in MAFLD. Full article