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 journalArticlepeer-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 languageEnglish (US)
Article number105431
JournaliScience
Volume25
Issue number11
DOIs
StatePublished - Nov 18 2022

Keywords

  • Biochemistry
  • Biological sciences
  • Immunology
  • Molecular biology

ASJC Scopus subject areas

  • General

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