Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration. 2017

Sarmistha Mukherjee, and Karthikeyani Chellappa, and Andrea Moffitt, and Joan Ndungu, and Ryan W Dellinger, and James G Davis, and Beamon Agarwal, and Joseph A Baur
Department of Physiology and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

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).

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008115 Liver Regeneration Repair or renewal of hepatic tissue. Liver Regenerations,Regeneration, Liver,Regenerations, Liver
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009243 NAD A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed) Coenzyme I,DPN,Diphosphopyridine Nucleotide,Nadide,Nicotinamide-Adenine Dinucleotide,Dihydronicotinamide Adenine Dinucleotide,NADH,Adenine Dinucleotide, Dihydronicotinamide,Dinucleotide, Dihydronicotinamide Adenine,Dinucleotide, Nicotinamide-Adenine,Nicotinamide Adenine Dinucleotide,Nucleotide, Diphosphopyridine
D009536 Niacinamide An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. Nicotinamide,Vitamin B 3,Vitamin PP,3-Pyridinecarboxamide,Enduramide,Nicobion,Nicotinsäureamid Jenapharm,Papulex,Vitamin B3,3 Pyridinecarboxamide,B 3, Vitamin,B3, Vitamin,Jenapharm, Nicotinsäureamid
D011726 Pyridinium Compounds Derivatives of PYRIDINE containing a cation C5H5NH or radical C5H6N. Compounds, Pyridinium
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random

Related Publications

Sarmistha Mukherjee, and Karthikeyani Chellappa, and Andrea Moffitt, and Joan Ndungu, and Ryan W Dellinger, and James G Davis, and Beamon Agarwal, and Joseph A Baur
April 1975, Biochimica et biophysica acta,
Sarmistha Mukherjee, and Karthikeyani Chellappa, and Andrea Moffitt, and Joan Ndungu, and Ryan W Dellinger, and James G Davis, and Beamon Agarwal, and Joseph A Baur
February 1968, The Journal of biological chemistry,
Sarmistha Mukherjee, and Karthikeyani Chellappa, and Andrea Moffitt, and Joan Ndungu, and Ryan W Dellinger, and James G Davis, and Beamon Agarwal, and Joseph A Baur
October 1974, Hoppe-Seyler's Zeitschrift fur physiologische Chemie,
Sarmistha Mukherjee, and Karthikeyani Chellappa, and Andrea Moffitt, and Joan Ndungu, and Ryan W Dellinger, and James G Davis, and Beamon Agarwal, and Joseph A Baur
April 1967, Biochimica et biophysica acta,
Sarmistha Mukherjee, and Karthikeyani Chellappa, and Andrea Moffitt, and Joan Ndungu, and Ryan W Dellinger, and James G Davis, and Beamon Agarwal, and Joseph A Baur
August 1964, The Journal of biological chemistry,
Sarmistha Mukherjee, and Karthikeyani Chellappa, and Andrea Moffitt, and Joan Ndungu, and Ryan W Dellinger, and James G Davis, and Beamon Agarwal, and Joseph A Baur
February 1965, Biochimica et biophysica acta,
Sarmistha Mukherjee, and Karthikeyani Chellappa, and Andrea Moffitt, and Joan Ndungu, and Ryan W Dellinger, and James G Davis, and Beamon Agarwal, and Joseph A Baur
November 1962, Plant physiology,
Sarmistha Mukherjee, and Karthikeyani Chellappa, and Andrea Moffitt, and Joan Ndungu, and Ryan W Dellinger, and James G Davis, and Beamon Agarwal, and Joseph A Baur
November 1993, Archives of biochemistry and biophysics,
Sarmistha Mukherjee, and Karthikeyani Chellappa, and Andrea Moffitt, and Joan Ndungu, and Ryan W Dellinger, and James G Davis, and Beamon Agarwal, and Joseph A Baur
January 1965, The Journal of biological chemistry,
Sarmistha Mukherjee, and Karthikeyani Chellappa, and Andrea Moffitt, and Joan Ndungu, and Ryan W Dellinger, and James G Davis, and Beamon Agarwal, and Joseph A Baur
March 1969, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme,
Copied contents to your clipboard!