Visfatin, Obesity, and Cancer
Cancer represents an important public health concern. Overweight, obesity, and metabolic syndrome influence the risk and prognosis of several disease states including cancer. Metabolic changes related to visceral obesity could contribute to a dysfunctiona
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Visfatin, Obesity, and Cancer Maria Dalamaga and Gerasimos Socrates Christodoulatos
Abstract Cancer represents an important public health concern. Overweight, obesity, and metabolic syndrome influence the risk and prognosis of several disease states including cancer. Metabolic changes related to visceral obesity could contribute to a dysfunctional adipose tissue provoking chronic subclinical inflammation, insulin resistance, and abnormal production of adipokines. Visfatin, found in the visceral adipose tissue, known also as nicotinamide phosphoribosyltransferase (Nampt) and pre-B-cell colony-enhancing factor (PBEF), acts as a multifaceted molecule with a triple action: a cytokine, a growth factor, and an enzyme. It exerts a pivotal role in a multitude of metabolic and stress responses and cellular bioenergetics, specifically nicotinamide adenine dinucleotide (NAD) synthesis. Visfatin/ Nampt exhibits antiapoptotic, proliferative, pro-inflammatory, pro-angiogenic, and metastatic properties. The insulin-mimetic function of visfatin/Nampt remains a controversial issue. Circulating visfatin/Nampt is enhanced in many cancers, including obesity-associated malignancies. It is associated with bad prognosis and higher tumor stage and grade. Plasma visfatin/Nampt may be a novel risk factor as well as a surrogate clinical marker in cancer therapeutics. Moreover, pharmacologic neutralization of visfatin/Nampt employing agents that reduce its levels or downregulate signaling pathways downstream of visfatin/Nampt could be promising anticancer treatments. In this book chapter, we will particularly focus on both intracellular and extracellular visfatin/Nampt’s contribution to cancer pathophysiology as well as on the mechanisms underlying the connection between visfatin/Nampt and cancer. Further research is required in order to conclude whether visfatin/Nampt may be a therapeutic target in the pharmacological arsenal for cancer.
M. Dalamaga, M.D., M.Sc., M.P.H., Ph.D. (*) Department of Clinical Biochemistry, University of Athens, “Attikon” General University Hospital, 1 Rimini Street, Chaidari, 12462 Athens, Greece Department of Biological Chemistry-Clinical Biochemistry, University of Athens Medical School, 75 Mikras Asias Street, Goudi, 11527 Athens, Greece e-mail: [email protected] G.S. Christodoulatos, M.D. Department of Clinical Biochemistry, University of Athens, “Attikon” General University Hospital, 1 Rimini Street, Chaidari, 12462 Athens, Greece e-mail: [email protected] © Springer International Publishing Switzerland 2017 O. Reizes, N.A. Berger (eds.), Adipocytokines, Energy Balance, and Cancer, Energy Balance and Cancer 12, DOI 10.1007/978-3-319-41677-9_6
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M. Dalamaga and G.S. Christodoulatos
Keywords Adipokine • Biomarker • Cancer • Nicotinamide phosphoribosyltransferase • Obesity • Pre-B-cell colony-enhancing factor • Visfatin
Abbreviations ADP ALL AML AMPK ATP BC BMI Cdks C.I. CLL CML CRP CtBPs ER ERKs HL ICAM-1 IL IGF IRS MAPK MDS MM MPD MMPs NAD Nampt NHL NF-kB OR PARP PBEF PI3K PTEN SirT SNPs
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