Title:Nesfatin-1 and the Cardiovascular System: Central and Pheripheral Actions and Cardioprotection
Volume: 16
Issue: 8
Author(s): Sandra Imbrogno, Tommaso Angelone and Maria C. Cerra
Affiliation:
Keywords:
Neuropeptides, cardiovascular physiology, 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.