Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide)

Julianna D. Zeidler; Claudia C.S. Chini; Karina S. Kanamori; Sonu Kashyap; Jair M. Espindola-Netto; Katie Thompson; Gina Warner; Fernanda S. Cabral; Thais R. Peclat; Lilian Sales Gomez; Sierra A. Lopez; Miles K. Wandersee; Renee A. Schoon; Kimberly Reid; Keir Menzies; Felipe Beckedorff; Joel M. Reid; Sebastian Brachs; Ralph G. Meyer; Mirella L. Meyer-Ficca; Eduardo Nunes Chini

doi:10.1016/j.isci.2022.105431

Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide)

Julianna D. Zeidler, Claudia C.S. Chini, Karina S. Kanamori, Sonu Kashyap, Jair M. Espindola-Netto, Katie Thompson, Gina Warner, Fernanda S. Cabral, Thais R. Peclat, Lilian Sales Gomez, Sierra A. Lopez, Miles K. Wandersee, Renee A. Schoon, Kimberly Reid, Keir Menzies, Felipe Beckedorff, Joel M. Reid, Sebastian Brachs, Ralph G. Meyer, Mirella L. Meyer-FiccaEduardo Nunes Chini

Research output: Contribution to journal › Article › peer-review

Abstract

In mammals, nicotinamide (NAM) is the primary NAD precursor available in circulation, a signaling molecule, and a precursor for methyl-nicotinamide (M-NAM) synthesis. However, our knowledge about how the body regulates tissue NAM levels is still limited. Here we demonstrate that dietary vitamin B₃ partially regulates plasma NAM and NAM-derived metabolites, but not their tissue levels. We found that NAD de novo synthesis from tryptophan contributes to plasma and tissue NAM, likely by providing substrates for NAD-degrading enzymes. We also demonstrate that tissue NAM is mainly generated by endogenous metabolism and that the NADase CD38 is the main enzyme that produces tissue NAM. Tissue-specific CD38-floxed mice revealed that CD38 activity on endothelial and immune cells is the major contributor to tissue steady-state levels of NAM in tissues like spleen and heart. Our findings uncover the presence of different pools of NAM in the body and a central role for CD38 in regulating tissue NAM levels.

Original language	English (US)
Article number	105431
Journal	iScience
Volume	25
Issue number	11
DOIs	https://doi.org/10.1016/j.isci.2022.105431
State	Published - Nov 18 2022

Keywords

Biochemistry
Biological sciences
Immunology
Molecular biology

ASJC Scopus subject areas

General

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10.1016/j.isci.2022.105431

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Zeidler, J. D., Chini, C. C. S., Kanamori, K. S., Kashyap, S., Espindola-Netto, J. M., Thompson, K., Warner, G., Cabral, F. S., Peclat, T. R., Gomez, L. S., Lopez, S. A., Wandersee, M. K., Schoon, R. A., Reid, K., Menzies, K., Beckedorff, F., Reid, J. M., Brachs, S., Meyer, R. G., ... Chini, E. N. (2022). Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide). iScience, 25(11), Article 105431. https://doi.org/10.1016/j.isci.2022.105431

Zeidler, JD, Chini, CCS, Kanamori, KS, Kashyap, S, Espindola-Netto, JM, Thompson, K, Warner, G, Cabral, FS, Peclat, TR, Gomez, LS, Lopez, SA, Wandersee, MK, Schoon, RA, Reid, K, Menzies, K, Beckedorff, F, Reid, JM, Brachs, S, Meyer, RG, Meyer-Ficca, ML & Chini, EN 2022, 'Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide)', iScience, vol. 25, no. 11, 105431. https://doi.org/10.1016/j.isci.2022.105431

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title = "Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide)",

abstract = "In mammals, nicotinamide (NAM) is the primary NAD precursor available in circulation, a signaling molecule, and a precursor for methyl-nicotinamide (M-NAM) synthesis. However, our knowledge about how the body regulates tissue NAM levels is still limited. Here we demonstrate that dietary vitamin B3 partially regulates plasma NAM and NAM-derived metabolites, but not their tissue levels. We found that NAD de novo synthesis from tryptophan contributes to plasma and tissue NAM, likely by providing substrates for NAD-degrading enzymes. We also demonstrate that tissue NAM is mainly generated by endogenous metabolism and that the NADase CD38 is the main enzyme that produces tissue NAM. Tissue-specific CD38-floxed mice revealed that CD38 activity on endothelial and immune cells is the major contributor to tissue steady-state levels of NAM in tissues like spleen and heart. Our findings uncover the presence of different pools of NAM in the body and a central role for CD38 in regulating tissue NAM levels.",

keywords = "Biochemistry, Biological sciences, Immunology, Molecular biology",

author = "Zeidler, {Julianna D.} and Chini, {Claudia C.S.} and Kanamori, {Karina S.} and Sonu Kashyap and Espindola-Netto, {Jair M.} and Katie Thompson and Gina Warner and Cabral, {Fernanda S.} and Peclat, {Thais R.} and Gomez, {Lilian Sales} and Lopez, {Sierra A.} and Wandersee, {Miles K.} and Schoon, {Renee A.} and Kimberly Reid and Keir Menzies and Felipe Beckedorff and Reid, {Joel M.} and Sebastian Brachs and Meyer, {Ralph G.} and Meyer-Ficca, {Mirella L.} and Chini, {Eduardo Nunes}",

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year = "2022",

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doi = "10.1016/j.isci.2022.105431",

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T1 - Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide)

AU - Zeidler, Julianna D.

AU - Chini, Claudia C.S.

AU - Kanamori, Karina S.

AU - Kashyap, Sonu

AU - Espindola-Netto, Jair M.

AU - Thompson, Katie

AU - Warner, Gina

AU - Cabral, Fernanda S.

AU - Peclat, Thais R.

AU - Gomez, Lilian Sales

AU - Lopez, Sierra A.

AU - Wandersee, Miles K.

AU - Schoon, Renee A.

AU - Reid, Kimberly

AU - Menzies, Keir

AU - Beckedorff, Felipe

AU - Reid, Joel M.

AU - Brachs, Sebastian

AU - Meyer, Ralph G.

AU - Meyer-Ficca, Mirella L.

AU - Chini, Eduardo Nunes

PY - 2022/11/18

Y1 - 2022/11/18

N2 - In mammals, nicotinamide (NAM) is the primary NAD precursor available in circulation, a signaling molecule, and a precursor for methyl-nicotinamide (M-NAM) synthesis. However, our knowledge about how the body regulates tissue NAM levels is still limited. Here we demonstrate that dietary vitamin B3 partially regulates plasma NAM and NAM-derived metabolites, but not their tissue levels. We found that NAD de novo synthesis from tryptophan contributes to plasma and tissue NAM, likely by providing substrates for NAD-degrading enzymes. We also demonstrate that tissue NAM is mainly generated by endogenous metabolism and that the NADase CD38 is the main enzyme that produces tissue NAM. Tissue-specific CD38-floxed mice revealed that CD38 activity on endothelial and immune cells is the major contributor to tissue steady-state levels of NAM in tissues like spleen and heart. Our findings uncover the presence of different pools of NAM in the body and a central role for CD38 in regulating tissue NAM levels.

AB - In mammals, nicotinamide (NAM) is the primary NAD precursor available in circulation, a signaling molecule, and a precursor for methyl-nicotinamide (M-NAM) synthesis. However, our knowledge about how the body regulates tissue NAM levels is still limited. Here we demonstrate that dietary vitamin B3 partially regulates plasma NAM and NAM-derived metabolites, but not their tissue levels. We found that NAD de novo synthesis from tryptophan contributes to plasma and tissue NAM, likely by providing substrates for NAD-degrading enzymes. We also demonstrate that tissue NAM is mainly generated by endogenous metabolism and that the NADase CD38 is the main enzyme that produces tissue NAM. Tissue-specific CD38-floxed mice revealed that CD38 activity on endothelial and immune cells is the major contributor to tissue steady-state levels of NAM in tissues like spleen and heart. Our findings uncover the presence of different pools of NAM in the body and a central role for CD38 in regulating tissue NAM levels.

KW - Biochemistry

KW - Biological sciences

KW - Immunology

KW - Molecular biology

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Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide)

Abstract

Keywords

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