NAD + repletion with niacin counteracts cancer cachexia.

Autor: Beltrà M; Experimental Medicine and Clinical Pathology Unit, Department of Clinical and Biological Sciences, University of Torino, Turin, Italy., Pöllänen N; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Fornelli C; Experimental Medicine and Clinical Pathology Unit, Department of Clinical and Biological Sciences, University of Torino, Turin, Italy., Tonttila K; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Faculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, Jyväskylä, Finland., Hsu MY; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Turin, Italy., Zampieri S; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.; Department of Biomedical Sciences, University of Padova, Padova, Italy.; CIR-MYO Myology Center, University of Padova, Padova, Italy., Moletta L; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy., Corrà S; Veneto Institute of Molecular Medicine, Padova, Italy., Porporato PE; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Turin, Italy., Kivelä R; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Faculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, Jyväskylä, Finland.; Wihuri Research Institute, Helsinki, Finland., Viscomi C; Department of Biomedical Sciences, University of Padova, Padova, Italy.; Study Centre for Neurodegeneration, University of Padova (CESNE), Padova, Italy., Sandri M; Department of Biomedical Sciences, University of Padova, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy., Hulmi JJ; Faculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, Jyväskylä, Finland., Sartori R; Department of Biomedical Sciences, University of Padova, Padova, Italy. roberta.sartori@unipd.it.; Veneto Institute of Molecular Medicine, Padova, Italy. roberta.sartori@unipd.it., Pirinen E; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. eija.pirinen@helsinki.fi.; Research Unit of Biomedicine and Internal Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland. eija.pirinen@helsinki.fi.; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. eija.pirinen@helsinki.fi., Penna F; Experimental Medicine and Clinical Pathology Unit, Department of Clinical and Biological Sciences, University of Torino, Turin, Italy. fabio.penna@unito.it.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 03; Vol. 14 (1), pp. 1849. Date of Electronic Publication: 2023 Apr 03.
DOI: 10.1038/s41467-023-37595-6
Abstrakt: Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD + ) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD + and downregulation of Nrk2, an NAD + biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD + repletion therapy in cachectic mice reveals that NAD + precursor, vitamin B3 niacin, efficiently corrects tissue NAD + levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD + in the pathophysiology of human cancer cachexia. Overall, our results propose NAD + metabolism as a therapy target for cachectic cancer patients.
(© 2023. The Author(s).)
Databáze: MEDLINE
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