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Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration
Journal article   Open access   Peer reviewed

Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration

Sarmistha Mukherjee, Karthikeyani Chellappa, Andrea Moffitt, Joan Ndungu, Ryan W Dellinger, James G Davis, Beamon Agarwal and Joseph A Baur
Hepatology (Baltimore, Md.), v 65(2), pp 616-630
Feb 2017
DOI: https://doi.org/10.1002/hep.28912
PMID: 27809334
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1002/hep.28912View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Animals Disease Models, Animal Fluorescent Antibody Technique Hepatectomy - methods Immunoblotting Immunohistochemistry Liver - drug effects Liver - pathology Liver Regeneration - drug effects Liver Regeneration - physiology Male Mice Mice, Inbred C57BL Mice, Transgenic NAD - biosynthesis NAD - metabolism Niacinamide - analogs & derivatives Niacinamide - pharmacology Random Allocation Sensitivity and Specificity
The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. To distinguish the role of hepatocyte NAD levels from any systemic effects of NR, we generated mice overexpressing nicotinamide phosphoribosyltransferase, a rate-limiting enzyme for NAD synthesis, specifically in the liver. Nicotinamide phosphoribosyltransferase overexpressing mice were mildly hyperglycemic at baseline and, similar to mice treated with NR, exhibited enhanced liver regeneration and reduced steatosis following partial hepatectomy. Conversely, mice lacking nicotinamide phosphoribosyltransferase in hepatocytes exhibited impaired regenerative capacity that was completely rescued by administering NR. NAD availability is limiting during liver regeneration, and supplementation with precursors such as NR may be therapeutic in settings of acute liver injury. (Hepatology 2017;65:616-630).

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Web of Science research areas
Gastroenterology & Hepatology
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