Expanding roles of NUCB2/nesfatin-1 in neuroendocrine regulation

Abstract

Nesfatin-1 was originally identified as a hypothalamic neuropeptide, derived from the precursor NEFA (for DNA binding/EF-hand/acidic protein)/nucleobindin 2 (NUCB2), with the ability to suppress food intake, acting in a leptin-independent manner. Departing from this seminal finding, the patterns of expression of NUCB2/nesfatin-1 have been thoroughly characterized in different hypothalamic nuclei and brain areas with proven roles in energy homeostasis, and its potential interactions with other key neuropeptide regulators of appetite have been documented. Intriguingly, recent experimental evidence suggests that NUCB2/nesfatin-1 is also expressed in peripheral tissues with relevant metabolic functions, such as the pancreas, the adipose, and the gut. In addition, evidence is mounting that nesfatin signaling may participate in adaptative responses and in the control of body functions gated by the state of energy reserves, such as puberty onset. Altogether, these observations have broadened our perception of the biological profile of nesfatin-1 that, rather than a simple anorectic signal in the hypothalamus, might operate at different tissues as an integral regulator of energy homeostasis and closely related neuroendocrine functions.

ENDOCRINOLOGY AND ADOLESCENCE: Deciphering puberty: novel partners, novel mechanisms

“…Yet, as highlighted elsewhere in this review, experimental work in different species has also defined the important contribution of other central transmitters and peripheral hormones, such as glutamate, GABA, and ghrelin (just to name but a few examples) in the physiological control of puberty onset (72,73). A recent addition to the growing list of pubertal modulators is nesfatin-1, as revealed by recent data on pubertal female rats (74,75). The major features of this neuropeptide as a putative regulator of the timing of puberty in the female are summarized below and synoptically presented in Table 3.…”

“…Nesfatin-1 is one of the peptide products of the gene NUCB2, with the ability to conduct anorectic effects acting at central (hypothalamic) levels (75). The interest in the metabolic actions of this molecule was reinforced by the demonstration of its expression in hypothalamic areas with key roles in food intake control, such as the ARC, the paraventricular nucleus (PVN), and the lateral hypothalamus (LHA), and the fact that anorectic effects of nesfatin-1 appear to be independent of leptin signaling (75).…”

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

“…In recent studies, increasing blood pressure effect of nesfatin-1 has been demonstrated (14,24,22). Yosten et al reported that intracerebroventricular injection of nesfatin 1 caused an increased blood pressure in rats (24).…”

“…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).…”

“…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.…”