Cth/Mpst double ablation results in early onset fatty liver disease in lean mice DOI Creative Commons
Antonia Katsouda,

M. Markou,

Dimitrios Valakos

и другие.

Redox Biology, Год журнала: 2025, Номер unknown, С. 103641 - 103641

Опубликована: Апрель 1, 2025

Metabolic dysfunction-associated fatty liver disease (MAFLD), a condition that stems from hepatic lipid accumulation in the absence of damage and overt inflammation, has become most common disorder worldwide. Hydrogen sulfide (H2S), gasotrasmitter, endogenously generated mainly by cystathionine-γ lyase (CTH), cystathionine-β synthase (CBS) 3-mercaptopyruvate sulfurtransferase (MPST) enzymes, exhibits protective effect steatosis. Herein, we have demonstrated CTH MPST play central role MAFLD pathogenesis. Young Cth/Mpst knockout (Cth/Mpst-/-) mice, fed normal diet, had increased mass caused enhanced accumulation. Decreased insulin glucose sensitivity was observed CTH/MPST-deficient mice. At cellular level, CTH/MPST inhibition resulted deposition uptake hepatocytes. Transcriptome analysis revealed significant upregulation cholesterol biosynthesis SREBP-related genes Cth/Mpst-/- Transcription factor enrichment differentially expressed between two genotypes, major impact LXR, RXR PPARA phenotype. Sulfide donor (SG1002) treatment attenuated Our findings underline importance produced H2S pathogenesis introduce mouse as new animal model early onset

Язык: Английский

Cth/Mpst double ablation results in early onset fatty liver disease in lean mice DOI Creative Commons
Antonia Katsouda,

M. Markou,

Dimitrios Valakos

и другие.

Redox Biology, Год журнала: 2025, Номер unknown, С. 103641 - 103641

Опубликована: Апрель 1, 2025

Metabolic dysfunction-associated fatty liver disease (MAFLD), a condition that stems from hepatic lipid accumulation in the absence of damage and overt inflammation, has become most common disorder worldwide. Hydrogen sulfide (H2S), gasotrasmitter, endogenously generated mainly by cystathionine-γ lyase (CTH), cystathionine-β synthase (CBS) 3-mercaptopyruvate sulfurtransferase (MPST) enzymes, exhibits protective effect steatosis. Herein, we have demonstrated CTH MPST play central role MAFLD pathogenesis. Young Cth/Mpst knockout (Cth/Mpst-/-) mice, fed normal diet, had increased mass caused enhanced accumulation. Decreased insulin glucose sensitivity was observed CTH/MPST-deficient mice. At cellular level, CTH/MPST inhibition resulted deposition uptake hepatocytes. Transcriptome analysis revealed significant upregulation cholesterol biosynthesis SREBP-related genes Cth/Mpst-/- Transcription factor enrichment differentially expressed between two genotypes, major impact LXR, RXR PPARA phenotype. Sulfide donor (SG1002) treatment attenuated Our findings underline importance produced H2S pathogenesis introduce mouse as new animal model early onset

Язык: Английский

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