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Hepatology
Article
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Hepatology
Article . 2016 . Peer-reviewed
License: Wiley Online Library User Agreement
Data sources: Crossref
Hepatology
Article . 2017
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Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration

Authors: Sarmistha, Mukherjee; Karthikeyani, Chellappa; Andrea, Moffitt; Joan, Ndungu; Ryan W, Dellinger; James G, Davis; Beamon, Agarwal; +1 Authors

Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration

Abstract

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. Conclusion: 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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Keywords

Male, Niacinamide, Immunoblotting, Fluorescent Antibody Technique, Mice, Transgenic, Pyridinium Compounds, NAD, Immunohistochemistry, Sensitivity and Specificity, Liver Regeneration, Mice, Inbred C57BL, Disease Models, Animal, Mice, Random Allocation, Liver, Animals, Hepatectomy

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    99
    popularity
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    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
99
Top 1%
Top 10%
Top 10%
bronze