Does Resveratrol Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)?

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3746 - 3746

Опубликована: Март 27, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is influenced by a variety of factors, including environmental and genetic factors. The most significant outcome the alteration free fatty acid triglyceride metabolism. Lipotoxicity, impaired autophagy, chronic inflammation, oxidative stress, as well coexisting insulin resistance, obesity, changes in composition gut microbiota, are also considered crucial factors pathogenesis MASLD. Resveratrol polyphenolic compound that belongs to stilbene subgroup. This review summarises available information on therapeutic effects resveratrol against has demonstrated promising antisteatotic, antioxidant, anti-inflammatory activities cells vitro animal studies. been associated with inhibiting NF-κB pathway, activating SIRT-1 AMPK pathways, normalizing intestinal microbiome, alleviating inflammation. However, clinical studies have yielded inconclusive results regarding efficacy hepatic steatosis or reducing any parameters found MASLD human patients. lack homogeneity between studies, low bioavailability resveratrol, population variability when compared models could be reasons for this.

Язык: Английский

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Tauroursodeoxycholic acid inhibits intestinal inflammation and barrier disruption in mice with non‐alcoholic fatty liver disease

British Journal of Pharmacology, Год журнала: 2017, Номер 175(3), С. 469 - 484

Опубликована: Ноя. 15, 2017

The gut-liver axis is associated with the progression of non-alcoholic fatty liver disease (NAFLD). Targeting and bile acid-based pharmaceuticals are potential therapies for NAFLD. effect tauroursodeoxycholic acid (TUDCA), a candidate drug NAFLD, on intestinal barrier function, inflammation, gut lipid transport microbiota composition was analysed in murine model NAFLD.The NAFLD mouse established by feeding mice high-fat diet (HFD) 16 weeks. TUDCA administered p.o. during last 4 expression levels tight junction genes, metabolic inflammatory genes were determined quantitative PCR. Tissue inflammation evaluated haematoxylin eosin staining. 16S rRNA gene sequencing.TUDCA administration attenuated HFD-induced hepatic steatosis, responses, obesity insulin resistance mice. Moreover, responses as manifested decreased histopathology scores cytokine levels. In addition, improved function increasing molecules solid chemical barrier. components involved ileum also reduced HFD-fed Finally, TUDCA-treated showed different compared that but similar to normal chow diet-fed mice.TUDCA attenuates ameliorating improving decreasing fat modulating composition.

Язык: Английский

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Metabolic liver disease in diabetes – From mechanisms to clinical trials

Metabolism, Год журнала: 2020, Номер 111, С. 154299 - 154299

Опубликована: Июнь 20, 2020

Non-alcoholic fatty liver disease (NAFLD) comprises (steatosis), non-alcoholic steatohepatitis (NASH) and fibrosis/cirrhosis may lead to end-stage failure or hepatocellular carcinoma. NAFLD is tightly associated with the most frequent metabolic disorders, such as obesity, syndrome, type 2 diabetes mellitus (T2DM). Both multisystem diseases share several common mechanisms. Alterations of tissue communications include excessive lipid later cytokine release by dysfunctional adipose tissue, intestinal dysbiosis ectopic fat deposition in skeletal muscle. On level, this leads insulin resistance due abnormal handling mitochondrial function. Over time, cellular oxidative stress activation inflammatory pathways, again supported multiorgan crosstalk, determine progression. Recent studies show that particularly severe resistant (SIRD) subgroup (cluster) associates its accelerated progression increases risk diabetes-related cardiovascular kidney diseases, underpinning critical role resistance. Consequently, lifestyle modification certain drug classes used treat T2DM have demonstrated effectiveness for treating NAFLD, but also some novel therapeutic concepts be beneficial both T2DM. This review addresses bidirectional relationship between mechanisms underlying relevance biomarkers improving diagnostic modalities identification subgroups at specific Also, metabolism-related drugs discussed light recent clinical trials. Finally, highlights challenges addressed future on context

Язык: Английский

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Prenatal Exposure to Perfluoroalkyl Substances Associated With Increased Susceptibility to Liver Injury in Children

Hepatology, Год журнала: 2020, Номер 72(5), С. 1758 - 1770

Опубликована: Авг. 1, 2020

Background and Aims Per‐ polyfluoroalkyl substances (PFAS) are widespread persistent pollutants that have been shown to hepatotoxic effects in animal models. However, human evidence is scarce. We evaluated how prenatal exposure PFAS associates with established serum biomarkers of liver injury alterations metabolome children. Approach Results used data from 1,105 mothers their children (median age, 8.2 years; interquartile range, 6.6‐9.1) the European Human Early‐Life Exposome cohort (consisting six existing population‐based birth cohorts France, Greece, Lithuania, Norway, Spain, United Kingdom). measured concentrations perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate, perfluorohexane perfluoroundecanoate maternal blood. assessed alanine aminotransferase, aspartate gamma‐glutamyltransferase child serum. Using Bayesian kernel machine regression, we found higher during pregnancy was associated enzyme levels also metabolomics through a targeted assay significant perturbations amino acid glycerophospholipid metabolism PFAS. A latent variable analysis identified profile at high risk (odds ratio, 1.56; 95% confidence interval, 1.21‐1.92) characterized by increased branched‐chain acids (valine, leucine, isoleucine), aromatic (tryptophan phenylalanine), glycerophospholipids (phosphatidylcholine [PC] aa C36:1 Lyso‐PC C18:1). Conclusions Developmental can contribute pediatric injury.

Язык: Английский

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Coordinated Modulation of Energy Metabolism and Inflammation by Branched-Chain Amino Acids and Fatty Acids

Frontiers in Endocrinology, Год журнала: 2020, Номер 11

Опубликована: Сен. 8, 2020

As important metabolic substrates, branched-chain amino acids (BCAA) and fatty (FAs) are able to participate in many significant physiological processes, such as mitochondrial biogenesis, energy metabolism, inflammation, along with intermediate metabolites generated their catabolism. The increased levels of BCAA can lead dysfunction by reducing biogenesis adenosine triphosphate (ATP) production interfering glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle (TCA) cycle, oxidation. directly activate mammalian target rapamycin (mTOR) signaling pathway induce insulin resistance, or function together acids. In addition, elevated canonical nuclear factor-κB (NF-κB) inflammasome, regulate disorders through upregulated inflammatory signals. This review will focus on mechanisms which modulate metabolism inflammation synergistically, may contribute discovering new targets for treatment diseases.

Язык: Английский

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