Articles producció científica> Bioquímica i Biotecnologia

Combined metabolic activators decrease liver steatosis by activating mitochondrial metabolism in hamsters fed with a high-fat diet

  • Dades identificatives

    Identificador: imarina:9230636
    Autors:
    Yang HMayneris-Perxachs JBoqué NDel Bas JMArola LYuan MTürkez HUhlén MBorén JZhang CMardinoglu ACaimari A
    Resum:
    Although the prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase, there is no effective treatment approved for this condition. We previously showed, in high-fat diet (HFD)-fed mice, that the supplementation of combined metabolic activators (CMA), including nicotinamide riboside (NAD+ precursor) and the potent glutathione precursors serine and N-acetyl-l-cysteine (NAC), significantly decreased fatty liver by promoting fat oxidation in mitochondria. Afterwards, in a one-day proof-of-concept human supplementation study, we observed that this CMA, including also L-carnitine tartrate (LCT), resulted in increased fatty acid oxidation and de novo glutathione synthesis. However, the underlying molecular mechanisms associated with sup-plementation of CMA have not been fully elucidated. Here, we demonstrated in hamsters that the chronic supplementation of this CMA (changing serine for betaine) at two doses significantly decreased hepatic steatosis. We further generated liver transcriptomics data and integrated these data using a liver-specific genome-scale metabolic model of liver tissue. We systemically determined the molecular changes after the supplementation of CMA and found that it activates mitochondria in the liver tissue by modulating global lipid, amino acid, antioxidant and folate metabolism. Our findings provide extra evidence about the beneficial effects of a treatment based on this CMA against NAFLD.
  • Altres:

    Autor segons l'article: Yang H; Mayneris-Perxachs J; Boqué N; Del Bas JM; Arola L; Yuan M; Türkez H; Uhlén M; Borén J; Zhang C; Mardinoglu A; Caimari A
    Departament: Bioquímica i Biotecnologia
    Autor/s de la URV: Arola Ferrer, Luis Maria
    Paraules clau: Transcriptomics Oxidative stress Nafld Mitochondrial metabolism Combined metabolic activators vitamin-c transcriptomics protects peroxisome obesity mitochondrial metabolism insulin-resistance expression disease deficiency combined metabolic activators acid oxidation
    Resum: Although the prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase, there is no effective treatment approved for this condition. We previously showed, in high-fat diet (HFD)-fed mice, that the supplementation of combined metabolic activators (CMA), including nicotinamide riboside (NAD+ precursor) and the potent glutathione precursors serine and N-acetyl-l-cysteine (NAC), significantly decreased fatty liver by promoting fat oxidation in mitochondria. Afterwards, in a one-day proof-of-concept human supplementation study, we observed that this CMA, including also L-carnitine tartrate (LCT), resulted in increased fatty acid oxidation and de novo glutathione synthesis. However, the underlying molecular mechanisms associated with sup-plementation of CMA have not been fully elucidated. Here, we demonstrated in hamsters that the chronic supplementation of this CMA (changing serine for betaine) at two doses significantly decreased hepatic steatosis. We further generated liver transcriptomics data and integrated these data using a liver-specific genome-scale metabolic model of liver tissue. We systemically determined the molecular changes after the supplementation of CMA and found that it activates mitochondria in the liver tissue by modulating global lipid, amino acid, antioxidant and folate metabolism. Our findings provide extra evidence about the beneficial effects of a treatment based on this CMA against NAFLD.
    Àrees temàtiques: Pharmacology & pharmacy Medicine, research & experimental Medicine (miscellaneous) General biochemistry,genetics and molecular biology Ciencias sociales Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Biochemistry & molecular biology
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    Adreça de correu electrònic de l'autor: lluis.arola@urv.cat
    Identificador de l'autor: 0000-0003-2767-1974
    Data d'alta del registre: 2024-07-27
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://www.mdpi.com/2227-9059/9/10/1440
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Biomedicines. 9 (10):
    Referència de l'ítem segons les normes APA: Yang H; Mayneris-Perxachs J; Boqué N; Del Bas JM; Arola L; Yuan M; Türkez H; Uhlén M; Borén J; Zhang C; Mardinoglu A; Caimari A (2021). Combined metabolic activators decrease liver steatosis by activating mitochondrial metabolism in hamsters fed with a high-fat diet. Biomedicines, 9(10), -. DOI: 10.3390/biomedicines9101440
    DOI de l'article: 10.3390/biomedicines9101440
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2021
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Biochemistry & Molecular Biology,Biochemistry, Genetics and Molecular Biology (Miscellaneous),Medicine (Miscellaneous),Medicine, Research & Experimental,Pharmacology & Pharmacy
    Transcriptomics
    Oxidative stress
    Nafld
    Mitochondrial metabolism
    Combined metabolic activators
    vitamin-c
    transcriptomics
    protects
    peroxisome
    obesity
    mitochondrial metabolism
    insulin-resistance
    expression
    disease
    deficiency
    combined metabolic activators
    acid oxidation
    Pharmacology & pharmacy
    Medicine, research & experimental
    Medicine (miscellaneous)
    General biochemistry,genetics and molecular biology
    Ciencias sociales
    Biochemistry, genetics and molecular biology (miscellaneous)
    Biochemistry, genetics and molecular biology (all)
    Biochemistry & molecular biology
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