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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Gut Microbiota and Metabolic Dysfunction-Associated Steatotic Liver Disease

Antioxidants, Journal Year: 2024, Volume and Issue: 13(11), P. 1386 - 1386

Published: Nov. 14, 2024

Background: The gut microbiota constitutes a complex microorganism community that harbors bacteria, viruses, fungi, protozoa, and archaea. human bacterial has been extensively proven to participate in metabolism, immunity, nutrient absorption. Its imbalance, namely “dysbiosis”, linked disordered metabolism. Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the features deranged metabolism leading cause cirrhosis hepatocellular carcinoma. Thus, there pathophysiological link between dysbiosis MASLD. Aims Methods: We aimed review literature data on composition its MASLD describe concept “gut–liver axis”. Moreover, we reviewed approaches for modulation treatment. Results: There consolidated evidence particular associated with stages. model explaining relationship bidirectional organization, physiopathology Oxidative stress keystones pathophysiology fibrosis generation. promising efficacy pre- probiotics reversing patients, therapeutic effects. Few yet encouraging fecal transplantation (FMT) are available literature. Conclusions: characteristic key target reversal treatment via diet, pre/probiotics, FMT remains treatment, prevention, reversal.

Language: Английский

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Metabolic dysfunction associated steatotic liver and kidney stones: what is going on?

Current Opinion in Nephrology & Hypertension, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Metabolic dysfunction associated steatotic liver disease (MASLD) is increasing throughout the world, affecting nearly one in three individuals. Kidney stone disease, which also increasing, with MASLD. Common risk factors for both, including obesity, diabetes, dyslipidemia, hypertension, and metabolic syndrome, are likely drivers of this association. We present here a review associations possible interconnections between these two common processes. Epidemiological studies discordant regarding impact sex on association MASLD incident risk. The nature kidney stones rarely taken into account.A favorable milieu uric acid formation may be created by lower urine pH resulting from defective ammonium production insulin resistance, MASLD.Endogenous oxalate synthesis, major factor calcium stones, increased via decline activity enzymes involved detoxification glyoxylate, immediate precursor oxalate. driving remain to elucidated. Potential mechanisms identified underlying include an increase both stones.

Language: Английский

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N6-Methyladenosine Modification in the Metabolic Dysfunction-Associated Steatotic Liver Disease

Nutrients, Journal Year: 2025, Volume and Issue: 17(7), P. 1158 - 1158

Published: March 27, 2025

Epigenetics of N6-methyladenine (m6A) modification may play a key role during the regulation various diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). The m6A has been shown to be accomplished via exploitation several players such as methyltransferases, demethylases, and/or methylation-binding molecules. Significantly, methylation can regulate eukaryotic transcriptome by affecting subcellular localization, splicing, export, stability, translation, and decay those RNAs. An increasing amount data designated that RNAs also modulate expression autophagy-related genes, which could control autophagy in hepatocytes. Oxidative stress with reactive oxygen species (ROS) induce RNA methylation, might associated mitochondrial (mitophagy) development MASLD. Therefore, both important roles regulating pathogenesis Comprehending relationship between mitophagy helpful for future therapeutic strategies against This review would advance understanding regulatory mechanisms modification, focusing on impact dysregulation

Language: Английский

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Advanced Liver Fibrosis Impairs Cardiorespiratory Fitness in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease

Digestive Diseases and Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Language: Английский

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The Management of Cardiometabolic Risk in MAFLD: Therapeutic Strategies to Modulate Deranged Metabolism and Cholesterol Levels

Medicina, Journal Year: 2025, Volume and Issue: 61(3), P. 387 - 387

Published: Feb. 23, 2025

Background and Objectives: Fatty Liver Disease is a major health problem worldwide. We can distinguish liver steatosis as non-associated or associated with chronic/acute alcohol consumption. These two entities share similar stages ranging from hepatic fat storage (namely, steatosis) to inflammation, necrosis, fibrosis until hepatocellular carcinoma (HCC). Over time, “Metabolic Associated Disease” (MAFLD) has replaced nonalcoholic fatty disease (NAFLD) nomenclature included cardiometabolic criteria in these patients definition. Thus, obesity, type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia are MAFLD features of the metabolic syndrome. Importantly, there not specific treatment for MAFLD, but therapeutic strategies that act on dysfunction related MAFLD. They reduce progression its complications. Materials Methods: For all reasons, we conducted narrative review literature, focused special regard cholesterol metabolism. Results: recently redefined condition better describes metabolism derangement responsible disease. This distinguishes NAFLD. In fact, diagnostic require presence together at least one following: T2DM, evidence disorder such hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension. As result, closely linked an increased risk. Current approaches be used this risk, focusing lifestyle interventions pharmacological strategies. Several treatments diagnosed mainly cholesterol-lowering remedies. Among these, Pro-protein Convertase Subtilisin/Kexin 9 inhibitors (PCSK9i) show most promising efficacy profile data lacking. Agonists GLP-1 receptor, Sodium-glucose cotransporter-2 (SGLT2i) Dipeptidyl Peptidase-4 (DPP-4i) have “ multi-hit action allowing their use also diabetic Conclusions: Lifestyle modifications, some nutraceuticals, statins, incretins, PCSK9i changed natural course significantly improved outcomes Emerging drugs, Bempedoic acid, overcome compliance statins’ controversial effect fibrosis. Finally, medications targeting insulin resistance allow strategic convoluted pathophysiology multiple steps, potential steatosis, necrosis and, sometimes even reverse

Language: Английский

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Mitochondrial mt12361A>G increased risk of metabolic dysfunction-associated steatotic liver disease among non-diabetes

World Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 31(10)

Published: Feb. 26, 2025

BACKGROUND Insulin resistance, lipotoxicity, and mitochondrial dysfunction contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). Mitochondrial impairs oxidative phosphorylation increases reactive oxygen species production, leading steatohepatitis hepatic fibrosis. Artificial intelligence (AI) is a potent tool for diagnosis risk stratification. AIM To investigate DNA polymorphisms in susceptibility MASLD establish an AI model screening. METHODS Multiplex polymerase chain reaction was performed comprehensively genotype 82 variants screening dataset (n = 264). The significant single nucleotide polymorphism validated independent cohort 1046) using Taqman® allelic discrimination assay. Random forest, eXtreme gradient boosting, Naive Bayes, logistic regression algorithms were employed construct MASLD. RESULTS In dataset, only mt12361A>G significantly associated with showed borderline significance patients 2-3 cardiometabolic traits compared controls validation (P 0.055). Multivariate analysis confirmed that factor [odds ratio (OR) 2.54, 95% confidence interval (CI): 1.19-5.43, P 0.016]. genetic effect non-diabetic group but not diabetic group. mt12361G carriers had 2.8-fold higher than A (OR 2.80, 95%CI: 1.22-6.41, 0.015). By integrating clinical features mt12361A>G, random forest outperformed other detecting [training area under receiver operating characteristic curve (AUROC) 1.000, AUROC 0.876]. CONCLUSION variant increased severity patients. supports management primary care settings.

Language: Английский

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Updated recommendations for the management of metabolic dysfunction–associated steatotic liver disease (MASLD) by the Latin American working group.

Annals of Hepatology, Journal Year: 2025, Volume and Issue: unknown, P. 101903 - 101903

Published: March 1, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading causes chronic globally. Based on 2023 definition, MASLD characterized by presence metabolic dysfunction and limited alcohol consumption (<140 grams/week for women, <210 men). Given significant burden in Latin America, this guidance was developed American Association Study Liver (ALEH) Working Group to address key aspects its clinical assessment therapeutic strategies. In ultrasonography recommended as initial screening tool hepatic steatosis due accessibility, while Fibrosis-4 (FIB-4) preferred fibrosis risk stratification, with further evaluation using more specific techniques (i.e., vibration-controlled transient elastography or Enhanced Fibrosis [ELF] test). A Mediterranean diet advised all patients, a target 7-10% weight loss those excess weight. Complete abstinence patients fibrosis, smoking cessation encouraged regardless stage. Pharmacological options should be tailored based steatohepatitis, weight, diabetes, including resmetirom, incretin-based therapies, pioglitazone, sodium-glucose cotransporter-2 inhibitors. Bariatric surgery may considered obesity unresponsive lifestyle medical interventions. Hepatocellular carcinoma cirrhotic consideration given advanced individual risk. Finally, routine cardiovascular proper diabetes prevention management remain crucial MASLD.

Language: Английский

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Resmetirom directly inhibits lipid accumulation in human liver-derived organoids

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

Published: March 1, 2025

Language: Английский

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Extra Virgin Olive Oil Phenolic Compounds: Modulating Mitochondrial Function and Protecting Against Chronic Diseases—A Narrative Review

Nutrients, Journal Year: 2025, Volume and Issue: 17(9), P. 1443 - 1443

Published: April 25, 2025

Background: Extra virgin olive oil (EVOO), an essential element of the Mediterranean diet (MedDiet), has demonstrated considerable potential in improving mitochondrial health and protecting against chronic diseases. This narrative review aims to explore how main phenolic compounds found EVOO—hydroxytyrosol, oleuropein, oleocanthal—contribute by reducing oxidative stress inflammation. Methods: A search for scientific evidence was carried out between October 2024 March 2025 different bibliographic databases such as PubMed, Web Science, Embase, SciSpace, ResearchRabbit databases. The strategy included combinations terms “extra oil”, “EVOO polyphenols”, “mitochondrial function”, “oxidative stress”, “inflammation”, “mitophagy”, “chronic diseases”. Preclinical, clinical, mechanistic studies were included, giving priority peer-reviewed publications. Results: shows some bioactive components EVOO activate cellular pathways, mTOR, AMPK sirtuins, which promote biogenesis, improve efficiency electron transport chain, protect DNA integrity. Furthermore, improves membrane fluidity integrity, ensuring its functionality efficiency. On other hand, nutrition literacy, important component health, is a critical determinant people’s eating behaviors. Conclusions: Although recent supports metabolic benefits on metabolism function, further nutritional intervention with these are recommended confirm their clinical relevance dietary tool aimed at preventing and/or delaying age-related

Language: Английский

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