Nesfatin-1, a unique regulatory neuropeptide of the brain

Abstract

Nesfatin-1, a newly discovered NUCB2-derived satiety neuropeptide is expressed in several neurons of forebrain, hindbrain, brainstem and spinal cord. This novel anorexigenic substance seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis. Nesfatin-1 immunoreactive cells are detectable in arcuate (ARC), paraventricular (PVN) and supraoptic nuclei (SON), where the peptide is colocalized with POMC/CART, NPY, oxytocin and vasopressin. The nesfatin-1 molecule interacts with a G-protein coupled receptor and its cytophysiological effect depends on inhibitory hyperpolarization of NPY/AgRP neurons in ARC and melanocortin signaling in PVN. Administration of nesfatin-1 significantly inhibits consumatory behavior and decreases weight gain in experimental animals. These recent findings suggest the evidence for nesfatin-1 involvement in other important brain functions such as reproduction, sleep, cognition and anxiety- or stress-related responses. The neuroprotective and antiapoptotic properties of nesfatin-1 were also reported. From the clinical viewpoint it should be noteworthy, that the serum concentration of nesfatin-1 may be a sensitive marker of epileptic seizures. However, the details of nesfatin-1 physiology ought to be clarified, and it may be considered suitable in the future, as a potential drug in the pharmacotherapy of obesity, especially in patients treated with antipsychotics and antidepressants. On the other hand, some putative nesfatin-1 antagonists may improve eating disorders.

Nesfatin Role as Possible New Anti Obesity Treatment

“…Ongoing pre-clinical data suggest the possible use of subcutaneous and intranasal routes of nesfatin-1 administration (Shimizu et al, 2009c), which needs to be further explored. Another important aspect to be unraveled is the weight loss upon chronic administration of nesfatin-1 (Li et al, 2010;Gonzalez et al, 2012;Li et al, 2013;Dong et al, 2013) and possible related changes in energy balance and/or basal metabolic rate (Foo et al, 2008;García-Galiano et al, 2010;Gonzales et al, 2011;Pałasz et al, 2012;Kerbel and Unniappan, 2012;García-Galiano et al, 2012;Ghanbari Niaki et al, 2013;Vas et al, 2013) for which studies so far are limited. In fact, nesfatin-1 has a remarkably prolonged effect on food intake and body temperature (Könczöl et al, 2012).…”

“…In fact, the details of nesfatin-1 physiology ought to be clarified, and it may be considered suitable in the future, as a potential drug in the pharmacotherapy of obesity. On the other hand, some putative nesfatin-1 antagonists may improve eating disorders (Pałasz et al, 2012) DISCLOSURE STATEMENT…”

Supplementation of apelin increase plasma levels of nesfatin-1 in normal and DOCA-salt hypertensive rats

“…Structural analyses revealed the presence of several conserved cleavage recognition sites for prohormone convertases (PC3/1 and PC2) within rat NUCB2/ nesfatin sequence, thus suggesting this to be a precursor that gives rise, by differential proteolytic processing, to several active pep-tides. The predicted (major) fragments of such processing were termed nesfatin-1, nesfatin-2, and nesfatin-3 (14,15). Nesfatin-2 and nesfatin-3, the fragments of NUCB2, have the same structure as the DNA structure of calcium binding proteins However, there is no information about the biological activity of these peptides (14,16,17,18).…”

“…In particular, nesfatin-1 seems to be released by the concerted actions of PC3/1 and PC2. Functional analyses of three potential fragments of nesfatin-1 molecule (namely, the Nterminal (N23), the C-terminal (C29), and the central (M30) fragments) revealed that the mid-fragment contains the active site for the anorectic effects of nesfatin-1 (15,19). It's reported that nesfatin-1 is a peptide secreted in the tissues of central and peripheral nervous system and involved in the regulation of homeostasis.…”

Is There any Association Between Nesfatin-1 and Generalized Anxiety Disorder?

“…Nesfatin-1 was discovered in 2006 by Oh-I et al 9 as an 82 amino acid polypeptide derived from the calcium and DNA-binding protein. Initially, nesfatin-1 emerged as the anorexigenic hormone that suppresses appetite 10,11 . Merali et al 12 have reported that nesfatin-1 may be involved in the mediation of anxiety and/or related responses.…”