Metabolic dysfunction-associated steatotic liver disease and its link to cancer

Metabolism, Journal Year: 2024, Volume and Issue: 160, P. 156004 - 156004

Published: Aug. 24, 2024

Language: Английский

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From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease

Annals of Hepatology, Journal Year: 2025, Volume and Issue: unknown, P. 101777 - 101777

Published: Jan. 1, 2025

Non-alcoholic fatty liver disease (NAFLD), now recognized as metabolic dysfunction-associated steatotic (MASLD), represents a significant and escalating global health challenge. Its prevalence is intricately linked to obesity, insulin resistance, other components of the syndrome. As our comprehension MASLD deepens, it has become evident that this condition extends beyond liver, embodying complex, multi-systemic with hepatic manifestations mirror broader landscape. This comprehensive review delves into critical interplay between gut-liver axis oxidative stress, elucidating their pivotal roles in etiology progression MASLD. Our analysis reveals several key findings: (1) Bile acid dysregulation can trigger stress through enhanced ROS production hepatocytes Kupffer cells, leading mitochondrial dysfunction lipid peroxidation; (2) Gut microbiota dysbiosis disrupts intestinal barrier function, allowing increased translocation endotoxins like LPS, which activate inflammatory pathways TLR4 signaling promote via NADPH oxidase activation; (3) The redox-sensitive transcription factors NF-κB Nrf2 serve crucial mediators axis, regulating responses orchestrating antioxidant defenses; (4) Oxidative stress-induced damage function creates destructive feedback loop, further exacerbating inflammation progression. These findings highlight complex interrelationship pathogenesis, suggesting potential therapeutic targets for management.

Language: Английский

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From adiposity to steatosis: metabolic dysfunction-associated steatotic liver disease, a hepatic expression of metabolic syndrome – current insights and future directions

Clinical Diabetes and Endocrinology, Journal Year: 2024, Volume and Issue: 10(1)

Published: Dec. 2, 2024

Language: Английский

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Hepatic HSD17B6 is dispensable for diet-induced fatty liver disease in mice

Biochemistry and Biophysics Reports, Journal Year: 2025, Volume and Issue: 41, P. 101924 - 101924

Published: Jan. 19, 2025

Language: Английский

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

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

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Platelet-activating cytokines potentially associated with MASLD-induced liver injury significantly decreased following CPAP therapy: A translational study using a fatty liver mouse model

Sleep Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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

Published: March 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.

Language: Английский

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Evaluation of Metabolic Dysfunction-Associated Fatty Liver Disease-Related Pathogenic Mechanisms in Human Steatotic Liver Cell-Based Model: Beneficial Effects of Prunus domestica L. subsp. syriaca Extract

Nutrients, Journal Year: 2025, Volume and Issue: 17(7), P. 1249 - 1249

Published: April 3, 2025

Background/Objectives: Disrupted glucose uptake, oxidative stress, and increased de novo lipogenesis are some of the key features metabolic dysfunction-associated fatty liver disease (MASLD). The modulation these pathogenic mechanisms using extracts from natural sustainable sources is a promising strategy to mitigate progression. This study aimed evaluate effects Prunus domestica L. subsp. syriaca extract on processes, taking advantage cell-based model steatotic hepatocytes (HepG2-OA) that recapitulates pathophysiological MASLD. Methods: HepG2-OA cell was generated by treating cells for 7 days with 100 μM oleic acid (OA). effect different concentrations (0.01, 0.1, 0.5, 1 mg/mL) P. assessed through MTT assay (cell viability), flow cytometry (glucose uptake reactive oxygen species, ROS, production), spectrophotometry (lipid accumulation), qRT-PCR (expression selected genes). Results: exhibited no cytotoxicity at any tested concentration after 24 48 h in cells. dose-dependent fashion both 6 h. Additionally, reduced lipid accumulation downregulated expression lipogenic genes (DGAT1 FASN). Furthermore, cells, ROS production stress-related (SOD CAT). Conclusions: positively modulated molecular associated metabolism, lipogenesis, supporting its potential as nutraceutical candidate MASLD management.

Language: Английский

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

Hepatology International, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

Language: Английский

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Pathogenic Mechanisms of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Associated Hepatocellular Carcinoma

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 428 - 428

Published: March 13, 2025

Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of deaths worldwide. The etiology HCC has now dramatically changed from viral hepatitis to metabolic dysfunction-associated steatotic liver disease (MASLD). main pathogenesis MASLD-related hepatic lipid accumulation hepatocytes, which causes chronic inflammation subsequent progression fibrosis. Chronic generates oxidative stress DNA damage in contribute genomic instability, resulting development HCC. Several molecular pathways are also linked MASLD. In particular, MAPK PI3K-Akt-mTOR upregulated MASLD, promoting survival proliferation cells. addition, MASLD been reported enhance patients with infection. Although there no approved medication for besides resmetirom USA, some preventive strategies onset Sodium-glucose cotransporter-2 (SGLT2) inhibitor, a class medications, exert anti-tumor effects on by regulating reprogramming. Moreover, CD34-positive cell transplantation improves fibrosis intrahepatic angiogenesis supplying various growth factors. Furthermore, exercise through an increase energy consumption as well changes chemokines myokines. this review, we summarize recent progress made pathogenic mechanisms MASLD-associated introduced new therapeutic preventing based

Language: Английский

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