Gut microbiota-derived indole compounds attenuate metabolic dysfunction-associated steatotic liver disease by improving fat metabolism and inflammation

Gut Microbes, Год журнала: 2024, Номер 16(1)

Опубликована: Фев. 1, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic disease, and its prevalence has increased worldwide in recent years. Additionally, there a close relationship between MASLD gut microbiota-derived metabolites. However, mechanisms of metabolites are still unclear. We demonstrated decreased indole-3-propionic acid (IPA) indole-3-acetic (IAA) feces patients with hepatic steatosis compared to healthy controls. Here, IPA IAA administration ameliorated inflammation an animal model WD-induced by suppressing NF-κB signaling pathway through reduction endotoxin levels inactivation macrophages. Bifidobacterium bifidum metabolizes tryptophan produce IAA, B. effectively prevents production IAA. Our study demonstrates that derived from microbiota have novel preventive or therapeutic potential for treatment.

Язык: Английский

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Unlocking the potential of THR-β agonist therapies: resmetirom’s chemistry, biology, and patent insights

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Язык: Английский

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TM7SF3 controls TEAD1 splicing to prevent MASH-induced liver fibrosis

Cell Metabolism, Год журнала: 2024, Номер 36(5), С. 1030 - 1043.e7

Опубликована: Апрель 25, 2024

Язык: Английский

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Dual-etiology MAFLD: the interactions between viral hepatitis B, viral hepatitis C, alcohol, and MAFLD

Hepatology International, Год журнала: 2024, Номер 18(S2), С. 897 - 908

Опубликована: Авг. 8, 2024

Язык: Английский

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Collagen-rich liver-derived extracellular matrix hydrogels augment survival and function of primary rat liver sinusoidal endothelial cells and hepatocytes

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 278, С. 134717 - 134717

Опубликована: Авг. 12, 2024

Liver sinusoidal endothelial cells (LSECs) are key targets for addressing metabolic dysfunction-associated steatotic liver disease (MASLD). However, isolating and culturing primary LSECs is challenging due to rapid dedifferentiation, resulting in loss of function. The extracellular matrix (ECM) likely plays a crucial role maintaining the fate function LSECs. In this study, we explored influence liver-ECM (L-ECM) on developed culture conditions that maintain differentiated vitro prolonged periods. Porcine liver-derived L-ECM, containing 34.9 % protein, 0.045 glycosaminoglycans, negligible residual DNA (41.2 ng/mg), was utilized rat generated hydrogels. Proteomic analyses molecular weight distribution proteins solubilized L-ECM revealed typical diverse ECM core matrisome, with abundant collagens. hydrogels showed suitable stiffness stress relaxation properties. Furthermore, demonstrated collagen-rich enhanced LSECs' hepatocytes' viability, reduced dedifferentiation rate addition, hepatocyte maintained longer by compared traditional culturing. These beneficial effects attributed bioactive macromolecules including collagens, mechanical microarchitectural properties

Язык: Английский

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From Nonalcoholic Fatty Liver Disease to Metabolic Dysfunction-Associated Steatotic Liver Disease: Out with the Old, in with the New

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(3), С. 880 - 880

Опубликована: Фев. 2, 2024

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic (CLD) affecting a quarter global population [...]

Язык: Английский

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

World Journal of Gastroenterology, Год журнала: 2025, Номер 31(10)

Опубликована: Фев. 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.

Язык: Английский

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Shared genetic architecture between metabolic dysfunction-associated steatotic liver disease and cardiometabolic traits comorbidities: a genome-wide pleiotropic and multi-omics study

Metabolism and Target Organ Damage, Год журнала: 2025, Номер 5(2)

Опубликована: Апрель 21, 2025

Aim: While cardiometabolic disorders and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexist, the genetic connections causes are not clearly understood. This study aimed to explore their shared architecture elucidate mechanisms driving comorbidity. Methods: Using summary statistics from genome-wide association studies (GWASs) on MASLD 29 traits (CMTs), we assessed correlation causality, identified loci, genes, pathways, cell types, tissues. Additionally, biological were uncovered using single-cell RNA sequencing data. Results: Significant correlations detected between 17 CMTs, encompassing diseases, glucose, lipids, adiposity, inflammatory markers, after adjusting for multiple testing (p .adjust < 0.05). Cross-trait analysis yielded a total of 166 risk SNPs (including those located in or near TRIB1 , LPL PNPLA3 GCKR PPARG ). Subsequent colocalization highlighted 73 loci associated with both rs429358 (APOE ) consistently prioritized HyPrColoc. Common genes (such as NPC1 MST1R TMBIM1 IRAK1BP1 L3MBTL3 RBM6 RGS19 ), significant enrichment cholesterol metabolism, glucose immune inflammation, long-term depression. Shared tissue-specific heritability was liver, adipose, artery, adrenal gland, brain tissue. Moreover, observed specific types (epicardial adipocytes, erythroid progenitor cells, hepatocytes, glial macrophages, monocytes, myeloid cells). The expressions APOE which showed significantly altered macrophages patients compared controls. Causality potential medications also explored. Conclusion: Multiple pathways contribute comorbidity disorders, lipid metabolism emerging critical factor. provides valuable insight into possible underlying offers directions future therapeutic innovations.

Язык: Английский

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Incretin-based therapy in the management of metabolic dysfunction-associated steatotic liver disease (MASLD): one piece of the puzzle: Editorial on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: A network meta-analysis”

Clinical and Molecular Hepatology, Год журнала: 2024, Номер 30(4), С. 649 - 652

Опубликована: Июль 23, 2024

Язык: Английский

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Pathogenesis and management of metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma: a narrative review

The Ewha Medical Journal, Год журнала: 2024, Номер 47(4)

Опубликована: Окт. 15, 2024

Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly recognized as a leading cause of hepatocellular carcinoma (HCC), the third-leading cancer mortality worldwide, driven by global obesity epidemic. Projected to become primary HCC 2030, MASH-HCC presents unique clinical challenges. This review examines its management, including surveillance strategies and treatment advances, discusses prospects overcome existing accounts for 10–20% cases, particularly in Western countries, with rising incidence due obesity. Risk factors include cirrhosis, diabetes, obesity, alcohol, smoking, genetic polymorphisms (e.g., PNPLA3), microbiome alterations. The pathogenesis involves fibrosis, immune dysfunction T-cell impairment), molecular changes. Prevention focuses on lifestyle modifications. Surveillance patients MASH cirrhosis crucial but hindered poor ultrasound sensitivity obese patients, necessitating alternative methods. Treatment mirrors that other types, comorbidities potentially reduced efficacy immunotherapy necessitate tailored approaches. becoming HCC, interventions prevention. Improved early detection are critical challenging obesity-related factors. Treatments align those potential differences require careful consideration. Key needs identifying drivers non-cirrhotic MASLD, developing preventive therapies, refining methods, tailoring treatments. Trials should specifically report outcomes enable personalized therapies. Further research needed understand dysfunction, optimize immunotherapies, identify predictive biomarkers.

Язык: Английский

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