iScience (Nov 2022)
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
Affiliations
- Julianna D. Zeidler
- Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA
- Claudia C.S. Chini
- Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA
- Karina S. Kanamori
- Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA
- Sonu Kashyap
- Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA
- Jair M. Espindola-Netto
- Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA
- Katie Thompson
- Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA
- Gina Warner
- Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA
- Fernanda S. Cabral
- Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA
- Thais R. Peclat
- Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA
- Lilian Sales Gomez
- Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA
- Sierra A. Lopez
- Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, School of Veterinary Medicine, Utah State University, Logan, UT 84332, USA
- Miles K. Wandersee
- Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, School of Veterinary Medicine, Utah State University, Logan, UT 84332, USA
- Renee A. Schoon
- Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
- Kimberly Reid
- Interdisciplinary School of Health of Sciences, University Ottawa Brain and Mind Research Institute, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada
- Keir Menzies
- Interdisciplinary School of Health of Sciences, University Ottawa Brain and Mind Research Institute, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada
- Felipe Beckedorff
- Sylvester Comprehensive Cancer Center, Department of Human Genetics, Biomedical Research Building, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Joel M. Reid
- Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
- Sebastian Brachs
- Charité – Universitätsmedizin Berlin, Department of Endocrinology and Metabolism, 10115 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Ralph G. Meyer
- Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, School of Veterinary Medicine, Utah State University, Logan, UT 84332, USA
- Mirella L. Meyer-Ficca
- Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, School of Veterinary Medicine, Utah State University, Logan, UT 84332, USA
- Eduardo Nunes Chini
- Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 11
p. 105431
Abstract
Summary: 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.
