Novel cardiac role for Nesfatin-1: identification and physiological characterization in the rat

Nesfatin-1, a peptidic fragment derived from nucleobindin 2 (NUCB2), is known for its anorexic effects. NUCB2 gene expression is regulated by nutritional status, indicating a regulatory role of peripheral Nesfatin-1 in energy homeostasis. Nesfatin-1 is able to cross the blood-brain barrier and this suggests that either peripheral sources can affect brain activity or that central Nesfastin-1 can regulate peripheral functions. However, its influence on alimentary behavior, its peripheral distribution and the endocrine release induce to hypothesize a role in the processes which accompany obesity. So far nothing is known concerning the role of Nesfatin-1 at cardiac level. By using Western Blotting techniques we identified, in rat cardiac extracts the presence of Nesfatin-1. Physiological analyses performed on isolated and Langendorff-perfused paced cardiac preparations revealed that exposure to Nesfatin-1 induces negative inotropic and lusitropic effects, without affecting coronaries. These effects involve particulate Guanylate Cyclase (pGC), PKG and are independent by NOS activation. Nesfatin-1 increased ERK1/2 phosphorylation, with no effects on AkT, eNOS, and nNOS phosphorylations, and protein S-Nitrosylation. In conclusion, we suggested that 1) the heart expresses Nesfatin-1; 2) Nesfatin-1 directly affects myocardial performance; 3) cardiac effects are mediated by the pGC/PKG pathway and ERK1/2.Results may pave the way to include Nesfatin-1 in the neuroendocrine modulators of the cardiac function and to encourage clarification of its clinical potential in the presence of nutrition-dependent physio-pathologic conditions, including obesity.