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)

iScience. 2022 Oct 23;25(11):105431. doi: 10.1016/j.isci.2022.105431. eCollection 2022 Nov 18.

Authors

Julianna D Zeidler^{1

2}, Claudia C S Chini^{1

2}, Karina S Kanamori^{1

2}, Sonu Kashyap^{1

2}, Jair M Espindola-Netto^{1

2}, Katie Thompson^{1

2}, Gina Warner^{1

2}, Fernanda S Cabral^{1

2}, Thais R Peclat^{1

2}, Lilian Sales Gomez^{1

2}, Sierra A Lopez³, Miles K Wandersee³, Renee A Schoon⁴, Kimberly Reid⁵, Keir Menzies⁵, Felipe Beckedorff⁶, Joel M Reid⁴, Sebastian Brachs^{7

8}, Ralph G Meyer³, Mirella L Meyer-Ficca³, Eduardo Nunes Chini^{1

2}

Affiliations

¹ Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
² Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA.
³ Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, School of Veterinary Medicine, Utah State University, Logan, UT 84332, USA.
⁴ Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
⁵ Interdisciplinary School of Health of Sciences, University Ottawa Brain and Mind Research Institute, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
⁶ Sylvester Comprehensive Cancer Center, Department of Human Genetics, Biomedical Research Building, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
⁷ Charité - Universitätsmedizin Berlin, Department of Endocrinology and Metabolism, 10115 Berlin, Germany.
⁸ DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.

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.

Abstract

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