Summary of Study ST002167

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001376. The data can be accessed directly via it's Project DOI: 10.21228/M8VH8V This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002167
Study TitleRemote solid cancers rewire hepatic nitrogen metabolism via host nicotinamide-N-methyltransferase (AML cells)
Study SummaryCancers disrupt host homeostasis in various manners but the identity of host factors underlying such disruption remains largely unknown. Here we show that nicotinamide-N-methyltransferase (NNMT) is a novel host factor that mediates metabolic dysfunction in the livers of cancer-bearing mice. Multiple solid cancers distantly increase expression of Nnmt and its product 1-methylnicotinamide (MNAM) in the liver. Multi-omics analyses reveal suppression of the urea cycle accompanied by accumulation of amino acids, and enhancement of uracil biogenesis in the livers of cancer-bearing mice. Importantly, genetic deletion of Nnmt leads to alleviation of these metabolic abnormalities, and buffers cancer-dependent weight loss and reduction of the voluntary wheel-running activity. Our data also demonstrate that MNAM is capable of affecting urea cycle metabolites in the liver. These results suggest that cancers up-regulate the hepatic NNMT pathway to rewire liver metabolism towards uracil biogenesis rather than nitrogen disposal via the urea cycle, thereby disrupting host homeostasis. Anionic polar metabolites (i.e., organic acids, sugar phosphates, nucleotides, etc.) were analyzed via IC/HR/MS/MS. Cationic polar metabolites (i.e., amino acids, bases, nucleosides, NAM, SAM, MNAM, SAH, me2PY, me4PY, etc) were analyzed via PFPP-LC/HR/MS/MS.
Institute
Tohoku University
Last NameKawaoka
First NameShinpei
Address4-1 Seiryo-cho, Sendai, Miyagi, 9808575, Japan
Emailkawaokashinpei@gmail.com
Phone0227178568
Submit Date2022-05-13
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2022-06-01
Release Version1
Shinpei Kawaoka Shinpei Kawaoka
https://dx.doi.org/10.21228/M8VH8V
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Culture conditions Treatment
SA2076214T1_14T1-conditioned media No treatment
SA2076224T1_34T1-conditioned media No treatment
SA2076234T1_44T1-conditioned media No treatment
SA2076244T1_24T1-conditioned media No treatment
SA207625cont_2Control No treatment
SA207626cont_3Control No treatment
SA207627control_1Control No treatment
SA207628cont_1Control No treatment
SA207629control_2Control No treatment
SA207630control_3Control No treatment
SA207631control_4Control No treatment
SA207635TNF200_3Control TNFalpha (200 ng/mL) treatment
SA207636TNF200_2Control TNFalpha (200 ng/mL) treatment
SA207637TNF200_1Control TNFalpha (200 ng/mL) treatment
SA207632TNF20_3Control TNFalpha (20 ng/mL) treatment
SA207633TNF20_2Control TNFalpha (20 ng/mL) treatment
SA207634TNF20_1Control TNFalpha (20 ng/mL) treatment
Showing results 1 to 17 of 17
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