NLRP1 is activated by palmitic acid and induced in human metabolic dysfunction-associated steatohepatitis DOI Open Access
Miriam Pinilla,

Eulalia Campos Baños,

María Antonia Martínez‐Sánchez

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

ABSTRACT Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent cause of worldwide. This progressive condition ranges from simple steatosis to a more advanced stage, known as metabolic steatohepatitis (MASH), which characterized by inflammation, hepatocellular ballooning, and hepatic steatosis. Several studies have demonstrated involvement inflammasomes in MASH development. Recently, NLRP1 inflammasome has gained attention an important sensor various human inflammatory conditions, though its role diseases like MASLD remains unclear. In this study, we identified significantly higher mRNA protein levels samples patients with compared those normal or livers. Furthermore, correlated palmitic acid (PA) levels. We also showed that expression mediated PA both HepG2 cells organoids. Importantly, found was activated PA, but not other saturated fatty acids myristic acid, PA-induced activation inhibited oleic acid. These findings uncover previously unknown liver. However, further research needed fully understand complex interactions between NLRP1, processes development MASLD.

Language: Английский

Metabolomic Hallmarks of Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease DOI Open Access
Diren Beyoğlu, Yury Popov, Jeffrey R. Idle

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12809 - 12809

Published: Nov. 28, 2024

From a detailed review of 90 experimental and clinical metabolomic investigations obesity metabolic dysfunction-associated steatotic liver disease (MASLD), we have developed hallmarks for both MASLD. Obesity studies were conducted in mice, rats, humans, with consensus biomarker groups plasma/serum being essential nonessential amino acids, energy metabolites, gut microbiota acylcarnitines lysophosphatidylcholines (LPC), which formed the basis six obesity. Additionally, mice rats shared elevated cholesterol, humans fatty VLDL/LDL, bile acids phosphatidylcholines (PC). MASLD had been performed hamsters, cows, geese, blunt snout breams, zebrafish, agreement between lay foundation five Furthermore, group higher LPC/PC cholesteryl esters, acylcarnitines, lysophosphatidylethanolamines/phosphatidylethanolamines (LPE/PE), triglycerides/diglycerides, metabolites. These aid understanding role played by development, inform mechanistic into underlying pathogenesis, are critical new metabolite-inspired therapies.

Language: Английский

Citations

6
Genotoxicity of putrescine and its effects on gene expression in HepG2 cell line DOI
F.D. Campos-Pereira, Letícia Gonçalves,

Raquel Vaz Hara Jardim

et al.

Toxicology in Vitro, Journal Year: 2025, Volume and Issue: unknown, P. 106048 - 106048

Published: March 1, 2025

Language: Английский

Citations

0
Metabolism, sex, and what lies beyond the scalpel in MASLD DOI Open Access
Zong‐Long Li, Yue Tang,

De-Long Qin

et al.

Metabolism and Target Organ Damage, Journal Year: 2025, Volume and Issue: 5(2)

Published: April 2, 2025

The discovery of the one-carbon metabolism-homocysteine-metabolic dysfunction-associated steatotic liver disease (OCM-Hcy-MASLD) axis has renewed our understanding MASLD-related primary cancer (PLC). Based on Suzuki et al.’s mathematical modeling findings diminished cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) expression in MASLD, this commentary analyzes recent regarding sex-specific variations their implications for surgical management. We highlight how integration OCM-Hcy pathway modulation with precise interventions could enhance perioperative outcomes long-term prognosis. emerging evidence suggests that targeted metabolic interventions, particularly those accounting sex differences, may complement traditional approaches by addressing systemic nature PLC. This paradigm shift from purely resection toward comprehensive regulation marks a significant advance precision medicine hepatobiliary surgery, potentially improving both safety oncological outcomes.

Language: Английский

Citations

0
Effect of incorporating tributyrin and tricaproin in milk replacer on the hepatic metabolome of calves DOI Creative Commons
Ícaro Rainyer Rodrigues de Castro, Morteza Hosseini Ghaffari, L.N. Leal

et al.

Journal of Dairy Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

This study investigated the effects of incorporating tributyrin (TB) and tricaproin (TC) in MR on liver metabolome dairy calves. Forty-five male calves (46.1 ± 4.6 kg BW; 2.1 0.63 d age; mean SD) were blocked order arrival at research facility. Within each block, randomly assigned to 3 treatments (n = 15 per group): (1) an containing milk fat serving as biolical reference for composition (MF), (2) a control (CON) blend vegetable fats, (3) (TRI) same mixture fats CON, which TB TC incorporated. All isoenergetic with 36% lactose, 27% fat, 24% protein DM basis. Calves housed individually received (13.5% solids) via nipple buckets twice daily 0630 1730 h. Daily allowance was 6.0 L from 1-5, 7.0 6-9, 8.0 10-35. had ad libitum access water chopped straw but no starter feed fed. On 35 after arrival, euthanized tissue samples collected analyzed using targeted metabolomics approach. Liquid chromatography flow injection electrospray ionization triple quadrupole mass spectrometry MxP® Quant 500 kit used. Distinct metabolic profiles emerged, principal component analysis (PCA) indicating differences between fed MF those other treatments, collectively accounting almost 50% total variation. Partial Least Squares Discriminant Analysis (PLS-DA) confirmed significant metabolomes treatments. Volcano plot showed that compared NC, 51 metabolites higher MF, including 34 phosphatidylcholines, 8 sphingomyelins, lysophosphatidylcholines, 1 ceramide, hexosylceramides, eicosapentaenoic acid (EPA) glycochenodeoxycholic (GUDCA), while lower, 2 sphingomyelin (SM C22:3), diacylglycerol (DG 16:0_18:2), lysophosphatidylcholine (lysoPC C18:2), nitrogen-containing compounds (putrescine serine) C5 acylcarnitine. In addition, when comparing TRI, 37 4 ceramides, EPA GUDCA, 7 putrescine valerylcarnitine (C5). Importantly, found CON suggesting effect metabolome. These results demonstrate (CON TRI) significantly modulate underscore importance addressing formulations optimize outcomes.

Language: Английский

Citations

0
Alterations in hepatic amino acid metabolism related to MASLD in individuals with obesity DOI
Armando Jesús Pérez-Díaz,

Inmaculada Ros‐Madrid,

María Antonia Martínez‐Sánchez

et al.

Journal of Physiology and Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

Language: Английский

Citations

0
Identification of taurine as a resistance-associated metabolite against Aeromonas salmonicida and its protective, immune-regulatory, and microbiota-shaping effects in turbot (Scophthalmus maximus) DOI Creative Commons
Patricia Pereiro, Alberto Falcó,

Marta Fernández-Oliver

et al.

Aquaculture, Journal Year: 2025, Volume and Issue: 608, P. 742721 - 742721

Published: May 20, 2025

Language: Английский

Citations

0
NLRP1 is activated by palmitic acid and induced in human metabolic dysfunction-associated steatohepatitis DOI Open Access
Miriam Pinilla,

Eulalia Campos Baños,

María Antonia Martínez‐Sánchez

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

ABSTRACT Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent cause of worldwide. This progressive condition ranges from simple steatosis to a more advanced stage, known as metabolic steatohepatitis (MASH), which characterized by inflammation, hepatocellular ballooning, and hepatic steatosis. Several studies have demonstrated involvement inflammasomes in MASH development. Recently, NLRP1 inflammasome has gained attention an important sensor various human inflammatory conditions, though its role diseases like MASLD remains unclear. In this study, we identified significantly higher mRNA protein levels samples patients with compared those normal or livers. Furthermore, correlated palmitic acid (PA) levels. We also showed that expression mediated PA both HepG2 cells organoids. Importantly, found was activated PA, but not other saturated fatty acids myristic acid, PA-induced activation inhibited oleic acid. These findings uncover previously unknown liver. However, further research needed fully understand complex interactions between NLRP1, processes development MASLD.

Language: Английский

Citations

0