Weissella viridescens Attenuates Hepatic Injury, Oxidative Stress, and Inflammation in a Rat Model of High-Fat Diet-Induced MASLD

Nutrients, Год журнала: 2025, Номер 17(9), С. 1585 - 1585

Опубликована: Май 5, 2025

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic disorder globally. Probiotic supplementation has shown promise in its prevention and treatment. Although Weissella viridescens, a lactic acid bacterium with immunomodulatory effects, antibacterial anti-inflammatory activities, there lack of direct evidence for role alleviating MASLD. This study aimed to investigate protective effects W. viridescens strain Wv2365, isolated from healthy human feces, high-fat diet (HFD)-induced rat model Methods: Rats were randomly assigned normal chow (NC), (HFD), HFD supplemented Wv2365 (Wv2365) groups. All groups fed their respective diets 8 weeks. During this period, NC received daily oral gavage PBS, while group Wv2365. Results: significantly reduced HFD-induced body weight gain, improved NAFLD activity scores, alleviated hepatic injury, restored lipid metabolism. A transcriptomic analysis revealed downregulation inflammation-related pathways, along decreased serum levels TNF-α, IL-1β, IL-6, MCP-1, LPS. also activated Nrf2/HO-1 antioxidant pathway, enhanced enzyme activities malondialdehyde levels. gut microbiota showed enrichment beneficial genera, including Butyricicoccus, Akkermansia, Blautia. Serum metabolomic profiling increased metabolites indole-3-propionic acid, indoleacrylic glycolithocholic acid. Conclusions: attenuates oxidative stress, inflammation high-fat-diet-induced MASLD, supporting potential as probiotic candidate modulation

Язык: Английский

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Conjugated Lithocholic Acid Activates Hepatic TGR5 to Promote Lipotoxicity and MASLD‐MASH Transition by Disrupting Carnitine Biosynthesis

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Май 8, 2025

Abstract Conjugated lithocholic acid (LCA) plays a critical role in the development of metabolic dysfunction‐associated steatotic liver disease (MASLD). In this process, hepatocyte inflammation‐caused upregulation its receptor, Takeda G protein‐coupled receptor 5 (TGR5) is crucial factor. Serum bile profiling shows an increase conjugated LCA, which correlates with severity. Depletion Gpbar1 hepatocytes significantly protects against progression from MASLD to steatohepatitis (MASH) that related LCA. vivo and vitro experiments indicate TGR5 activation promotes lipotoxicity‐induced cell death inflammation by suppressing de novo carnitine biosynthesis. Mechanistically, binding CD36 facilitates E3 ubiquitin ligase TRIM21 recruitment, leading degradation BBOX1, enzyme Targeting therapeutically can restore biosynthesis, may offer potent strategy prevent or reverse transition MASH.

Язык: Английский

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Letter: Different Risk of Acute Variceal Bleeding According to the Liver Disease Aetiology in Decompensated Cirrhosis Patients Receiving Carvedilol‐Based Primary Prophylaxis—May Insulin Resistance Unloose This Gordian Knot?

Alimentary Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Май 13, 2025

Язык: Английский

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Molecular insights into herbal medicines for the treatment of metabolic associated Steatohepatitis

Discover Chemistry., Год журнала: 2025, Номер 2(1)

Опубликована: Май 25, 2025

Язык: Английский

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Genetic predisposition of metabolic dysfunction-associated steatotic liver disease: a population-based genome-wide association study

Hepatology International, Год журнала: 2025, Номер unknown

Опубликована: Янв. 5, 2025

Язык: Английский

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Challenges in Histological Endpoints for MASH Therapies: An Exercise in Statistical Modelling

Alimentary Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

ABSTRACT Background Regulatory‐accepted efficacy endpoints for nonalcoholic steatohepatitis (NASH; recently updated to metabolic‐dysfunction associated steatohepatitis, MASH) clinical trials include fibrosis improvement with no worsening of NASH or resolution determined by liver biopsy using the Clinical Research Network criteria. These involve scoring four histology parameters, all which are significant inter−/intra‐reader variability. Since few have shown positive results these endpoints, we evaluated effects imprecision in histologic on trial from a statistical perspective. Methods Estimating probability (sensitivity) accurately is based relationship between measures agreement and sensitivity. We simulated kappa values range sensitivities. Then, published trials, selected corresponding sensitivities parameters. Finally, simulations assuming “overscore” “underscore” probabilities were conducted estimate dilution true effect size. Results Simulations 2‐arm sample sizes 400 (mix stage 2/3 fibrosis) subjects showed ~50% size both approvable due imprecision. Such remains constant regardless Conclusion Imprecise disproportionately impacts ‘superior’ arm as error proportional response rate. This should be considered when weighing benefit overall risk–benefit profile review studies. argues adoption non‐invasive biomarkers rather than endpoints.

Язык: Английский

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Significance of FXR agonists in MASLD treatment: a deep dive into lipid alteration by analytical techniques

Опубликована: Март 25, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as a global health crisis, affecting over 30% of the population and demanding urgent attention. This redefined condition, previously known non-alcoholic fatty (NAFLD), reflects deeper understanding intricate interplay between metabolic dysfunction health. At heart MASLD lies troubling accumulation triglycerides (TGs) in hepatocytes, which precipitates insulin resistance oxidative stress, ultimately leading to more severe forms like steatohepatitis (MASH). Excitingly, recent research has spotlighted farnesoid X receptor (FXR) groundbreaking therapeutic target. FXR not only regulates lipid metabolism but also combats inflammation resistance, making it potential game-changer fight against MASLD. With one FDA-approved drug, resmetirom, currently available, exploration agonists opens new avenues for innovative treatments that could revolutionize patient care. By harnessing power restore balance integrating advanced strategies lipidomics acid profiling, we stand on brink transforming how approach its associated complications, paving way healthier future. review delves into promising role combating implications related disorders, emphasizing urgency detect manage this burgeoning epidemic.

Язык: Английский

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Editorial: Chrononutrition and MASLD—It is About Time (Restricted Feeding)! Authors' Reply

Alimentary Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

We sincerely appreciate the opportunity to respond editorial by Mohr and Stine discussing our study on effects of a 12-week Mediterranean-type time-restricted feeding (TRF) protocol in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) [1, 2]. are grateful for their insightful commentary highlighting strengths randomised controlled trial (RCT). Their analysis underscores emerging role chrononutrition managing MASLD while also key questions regarding independent contribution TRF caloric restriction improvements. There is indeed great need studies that directly compare ad libitum protocols evaluate differentiative impact several parameters. Most have compared either usual dietary habits participants or hypocaloric diets both control groups, as study. Our was first RCT used Mediterranean Diet (MD) group, gold standard [3]. The MD has been extensively documented an effective intervention [4]. adds this body evidence demonstrating MD, even over short-term period, yields significant improvements weight, fat, blood pressure fat content [1]. Regarding comment generalizability results [2], it true Greece country, described previous studies, Greeks' adherence moderate [5]. [1] agree these [5] may enhanced participants' adherence. interventions (early late) did not seem improve parameters mentioned above further population However, insulin resistance haemoglobin A1c (HbA1c) were only improved early but late group. reduction HbA1c group (0.3% total, 0.37% those T2DM under TRF) greater than other similar example, 0.2% Wei et al. + group) [6], whilst grade improvement associated lower mortality individuals [7] diabetic complications [8]. Prior suggest aligning food intake circadian rhythms light/dark cycle via enhance glucose metabolism humans diurnal [9]. This particularly relevant patients, where pivotal driver progression [10]. That means differences observed probably due intervention, all groups had same restriction. would like thank authors thoughtful comments, which allowed us refine interpretation highlight robustness findings. Future research will provide answers raised concerns. Sofia Tsitsou: writing – original draft, investigation, methodology, data curation. Magdalini Adamantou: curation, investigation. Triada Bali: Aristi Saridaki: Kalliopi-Anna Poulia: methodology. Dimitrios S. Karagiannakis: Emilia Papakonstantinou: Evangelos Cholongitas: conceptualization, review editing, project administration, supervision, visualization, draft. declare no conflicts interest. article linked Tsitsou al papers. To view articles, visit https://doi.org/10.1111/apt.70044 https://doi.org/10.1111/apt.70078. support findings available request from corresponding author. publicly privacy ethical restrictions.

Язык: Английский

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MetALD: New Perspectives on an Old Overlooked Disease

Liver International, Год журнала: 2025, Номер 45(5)

Опубликована: Апрель 3, 2025

ABSTRACT Metabolic dysfunction‐associated steatotic liver disease (MASLD) and alcohol‐associated (ALD) are the major contributors to burden globally. The rise in these conditions is linked obesity, type 2 diabetes, metabolic syndrome increased alcohol consumption. MASLD ALD share risk factors, pathophysiology histological features but differ their thresholds for use, definition does not require presence of dysfunction. A recent multi‐society consensus overhauled nomenclature steatosis introduced term MetALD describe patients with dysfunction who drink more than those less ALD. This new terminology aims enhance understanding management poses challenges, such as need accurately measure consumption research clinical practice settings. Recent studies show that has significant implications patient management, it associated mortality risks severe outcomes compared alone. face progression, cancer cardiovascular disease. diagnosis involves adequate quantification use through standardised questionnaires and/or biomarkers well proper assessment stage progression using non‐invasive tools including serologic markers, imaging, elastography techniques genetic testing. Effective requires addressing both alcohol‐related factors improve outcomes. review intends provide a comprehensive overview MetALD, covering pathogenesis, potential diagnostic approaches, strategies emerging therapies.

Язык: Английский

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Identification of pediatric MASLD using insulin resistance indices

JHEP Reports, Год журнала: 2025, Номер unknown, С. 101419 - 101419

Опубликована: Апрель 1, 2025

Язык: Английский

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