title: Nesfatin-1 and the Cardiovascular System: Central and Pheripheral Actions and Cardioprotection.
abstract: Recently, the hypothalamic 82-aa peptide Nesfatin-1 received notable attention for its anorexigenic and anti-hyperglycemic properties. In mammalian hypothalamus, Nesfatin-1 is expressed, together with the precursor Nucleobindin 2 (NUCB2), in regions controlling water-food intake, body weight, and glucose homeostasis. The peptide is also peripherally expressed, as shown in the rat heart, in which it is present together with NUCB2. In addition to a central modulation of nutrition and energy balance, and of the nervous circuits responsible for blood pressure and heart rate control, Nesfatin-1 also acts peripherally on several districts, including the cardiovascular (CV) system. Accordingly, the peptide is regarded with interest as a multifunctional hormone not only linked to alimentary homeostasis. This review aims to analyze the literature on Nesfatin-1, with focus on its emerging CV activity. Few available studies show that the peptide affects energy metabolism of murine and human cardiomyocytes, by eliciting insulin-like effects. On the ex vivo rat heart, it directly depresses contractility and relaxation via cGMP, PKG and ERK1/2, and limits ischemia/reperfusion (I/R) damage, acting in post-conditioning protection. Nesfatin-1 actions are proposed to involve an unknown G-protein coupled receptor. However, in the rat heart, functional studies, co-immunoprecipitation and local sequence alignment analyses suggest an interaction with the Natriuretic Peptide Receptor-type A (NPR-A). These data open up novel perspectives to clarify not only the biological significance of the peptide, but also its putative biomedical potential in the presence of nutrition-dependent cardiovascular diseases.
authors: Sandra
authors: S
authors: Imbrogno
authors: Lab of Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036, Arcavacata di Rende (CS)- Italy. tommaso.angelone@unical.it.
authors: Tommaso
authors: T
authors: Angelone
authors: Maria C
authors: MC
authors: Cerra
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D006801:Humans; D057775:Ischemic Postconditioning / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000080866:Nucleobindins; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; D002316:Cardiotonic Agents; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A