Regulation and Function of Extracellular Nicotinamide Phosphoribosyltransferase/Visfatin.
Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine-enzyme, which was described as to play bioactivities both in the intracellular and in the extracellular environment. However, while the functions of intracellular NAMPT (iNAMPT) are well known, much less is known on extracellular NAMPT (eNAMPT), also called visfatin or pre-B cell colony-enhancing factor. iNAMPT catalyzes the rate-limiting step in the NAD+ biosynthesis pathway from nicotinamide. Its inhibition severely reduces intracellular NAD+ levels, achieving anti-inflammatory and anti-cancer effects. eNAMPT can be detected in the human circulation and in many extracellular environments. Studies show that eNAMPT can act as a growth factor, as an enzyme, and as a cytokine, but its true mechanism of secretion and its physiological functions are still debated. Increased levels of eNAMPT have been associated with different metabolic disorders and cancers. eNAMPT was demonstrated to modulate the pathways involved in the pathophysiology of obesity, diabetes, atherosclerosis, and cardiovascular events by regulating the oxidative stress response, apoptosis, and inflammation. In cancer, eNAMPT was shown to play a pivotal role in modulating cancer cell metabolism, in promoting epithelial-to-mesenchymal transition and in shaping the tumor microenvironment. In line with these functions, circulating eNAMPT levels are frequently increased in cancer patients. Given these pleiotropic roles of eNAMPT in human disease, this protein has attracted attention as a therapeutic target. In this narrative review, we will discuss recent evidence on eNAMPT-driven signalling, highlighting the emerging pathophysiological roles of this protein in different disorders and the potential therapeutic opportunities linked to its targeting. © 2017 American Physiological Society. Compr Physiol 7:603-621, 2017.
First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Federico
F
Carbone
First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Luca
L
Liberale
First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Aldo
A
Bonaventura
First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Alessandra
A
Vecchiè
First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Matteo
M
Casula
Department of Internal Medicine, University of Genoa, Genoa, Italy.|IRCCS AOU San Martino-IST, Genoa, Italy.
Michele
M
Cea
Department of Internal Medicine, University of Genoa, Genoa, Italy.|IRCCS AOU San Martino-IST, Genoa, Italy.
Fiammetta
F
Monacelli
Department of Internal Medicine, University of Genoa, Genoa, Italy.
Irene
I
Caffa
Department of Experimental Medicine, University of Genoa, Genoa, Italy.|Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy.
Santina
S
Bruzzone
First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.|IRCCS AOU San Martino-IST, Genoa, Italy.|Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy.
Fabrizio
F
Montecucco
Department of Internal Medicine, University of Genoa, Genoa, Italy.|IRCCS AOU San Martino-IST, Genoa, Italy.
Alessio
A
Nencioni
D050197:Atherosclerosis / Q000201:enzymology; D016207:Cytokines / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology; D005110:Extracellular Space / Q000201:enzymology; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D018836:Inflammation Mediators / Q000502:physiology; D008659:Metabolic Diseases / Q000201:enzymology; D009369:Neoplasms / Q000201:enzymology; D054409:Nicotinamide Phosphoribosyltransferase / Q000502:physiology*; D015427:Reperfusion Injury / Q000201:enzymology; D015398:Signal Transduction / Q000502:physiology
D016207:Cytokines; D018836:Inflammation Mediators; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human