Author, as appears in the 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
Department: Bioquímica i Biotecnologia
URV's Author/s: Arola Ferrer, Luis Maria
Keywords: 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
Abstract: 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.
Thematic Areas: 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
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: lluis.arola@urv.cat
Author identifier: 0000-0003-2767-1974
Record's date: 2023-03-06
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.mdpi.com/2227-9059/9/10/1440
Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Biomedicines. 9 (10):
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
Article's DOI: 10.3390/biomedicines9101440
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications
Repositori URV