MetaboLights MTBLS368 - GNPS "Nicotinamide Riboside is Uniquely Bioavailable in People and Mice"
Ontology highlight
ABSTRACT:
INSTRUMENT(S): ACQUITY TQD (Waters)
ORGANISM(S): Blank Homo Sapiens Reference Compound Mus Musculus
SUBMITTER: 
Brenner
PROVIDER: MSV000082797 | GNPS | Tue Aug 07 16:42:00 BST 2018
REPOSITORIES: GNPS
Similar Datasets
Project description:Nicotinamide riboside (NR) is in wide use as an NAD+ precursor vitamin. Here we conducted experiments to determine the time and dose-dependent effects of NR on blood, liver and heart NAD+ metabolism in people and mice. We report that human blood cell NAD+ can rise as much as 2.7-fold with a single dose of NR, that NR elevates mouse hepatic NAD+ with distinct and superior pharmacokinetics to those of nicotinic acid (NA) and nicotinamide (Nam), and that single doses of 100, 300, and 1000 mg of NR provide a dose-dependent increase in the blood cell NAD+ metabolome in the first clinical trial of NR pharmacokinetics. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for conversion of NR to NAD+, is formed from NR and that the rise in NAAD is a highly sensitive biomarker of effective NAD+ supplementation.
2016-09-09 | MTBLS368 | MetaboLights
Project description:<p>NAMPT plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells was associated with down-regulation of genes relevant to QPRT-dependent de novo NAD synthesis, promoting NAMPTi susceptibility in vitro. We also found that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but NMRK1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations was synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma.</p><p><br></p><p><strong>Mouse NAMPT targeted therapy</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS7252' rel='noopener noreferrer' target='_blank'><strong>MTBLS7252</strong></a>.</p><p><strong>Cell NAMPTi treatment </strong>is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7251' rel='noopener noreferrer' target='_blank'><strong>MTBLS7251</strong></a>.</p><p><strong>Mouse NAD targeted time-course</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7253' rel='noopener noreferrer' target='_blank'><strong>MTBLS7253</strong></a>.</p>
2023-10-10 | MTBLS7252 | MetaboLights
Project description:<p>NAMPT plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells was associated with down-regulation of genes relevant to QPRT-dependent <em>de novo</em> NAD synthesis, promoting NAMPTi susceptibility <em>in vitro</em>. We also found that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but NMRK1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations was synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma.</p><p><br></p><p><strong>Cell NAMPTi treatment </strong>is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS7251' rel='noopener noreferrer' target='_blank'><strong>MTBLS7251</strong></a>.</p><p><strong>Mouse NAMPT targeted therapy</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7252' rel='noopener noreferrer' target='_blank'><strong>MTBLS7252</strong></a>.</p><p><strong>Mouse NAD targeted time-course</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7253' rel='noopener noreferrer' target='_blank'><strong>MTBLS7253</strong></a>.</p>
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Project description:<p>NAMPT plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells was associated with down-regulation of genes relevant to QPRT-dependent de novo NAD synthesis, promoting NAMPTi susceptibility in vitro. We also found that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but NMRK1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations was synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma.</p><p><br></p><p><strong>Mouse NAD targeted time-course</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS7253' rel='noopener noreferrer' target='_blank'><strong>MTBLS7253</strong></a>.</p><p><strong>Cell NAMPTi treatment</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7251' rel='noopener noreferrer' target='_blank'><strong>MTBLS7251</strong></a>.</p><p><strong>Mouse NAMPT targeted therapy</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7252' rel='noopener noreferrer' target='_blank'><strong>MTBLS7252</strong></a>.</p>
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Project description:Epithelial-mesenchymal transition (EMT) is a key cellular process involved in development and disease progression. Single-cell transcriptomes can reveal intermediate EMT states observed in tumors, but previous studies focused on time-dependent responses in epithelial cells after stimulation with EMT signals as an in vitro model for understanding EMT progression, so it was unclear how transcriptomes can change in response to different levels of EMT inducer. Here, we performed single-cell RNA-sequencing with human mammary epithelial cells treated with various concentrations of TGF-β. We found that the dose-dependent EMT harbors multiple intermediate states at the single-cell level after two weeks of treatment, suggesting a stable EMT continuum. After correcting batch effects from experiments, we performed comparative analyses of the dose- and time-dependent EMT. We found that the dose-dependent EMT shows a stronger anti-correlation between epithelial and mesenchymal transcriptional programs and a better resolution of stages of EMT compared to the time-dependent progress. These properties enable more power to detect genes whose expressions are associated with EMT. Nonetheless, our analyses showed cell clusters unique to the time-dependent EMT, which correspond to en route cell populations that do not appear at steady states. Furthermore, combining dose- and time-dependent cell clusters gave rise to more accurate prognosis for cancer patients compared to individual EMT spectrum.
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