Nesfatin-1--role as possible new potent regulator of food intake

Abstract

Nesfatin-1 is an 82 amino acid peptide recently discovered in the brain which is derived from nucleobindin2 (NUCB2), a protein that is highly conserved across mammalian species. Nesfatin-1 has received much attention over the past two years due to its reproducible food intake-reducing effect that is linked with recruitment of other hypothalamic peptides regulating feeding behavior. A growing amount of evidence also supports that various stressors activate fore- and hindbrain NUCB2/nesfatin-1 circuitries. In this review, we outline the central nervous system distribution of NUCB2/nesfatin-1, and recent developments on the peripheral expression of NUCB2/nesfatin-1, in particular its co-localization with ghrelin in gastric X/A-like cells and insulin in ss-cells of the endocrine pancreas. Functional studies related to the characteristics of nesfatin-1's inhibitory effects on dark phase food intake are detailed as well as the central activation of NUCB2/nesfatin-1 immunopositive neurons in the response to psychological, immune and visceral stressors. Lastly, potential clinical implications of targeting NUCB2/nesfatin-1 signaling and existing gaps in knowledge to ascertain the role and mechanisms of action of nesfatin-1 are presented.

Fig. 1

Expression of NUCB2/nesfatin-1 immunoreactivity in specific brain nuclei in rats and potential implication in various biological actions. Expression of NUCB2/nesfatin-1 immunoreactivity in the central amygdaloid nucleus and insular cortex are not shown due to the sagittal level displayed here. 3v, third ventricle; 4v, fourth ventricle; ARC, arcuate nucleus; DMH, dorsomedial nucleus of the hypothalamus; DMV, dorsal motor nucleus of the vagus nerve; DR, dorsal raphe nucleus; EW, Edinger-Westphal nucleus; LC, locus coeruleus; LHA, lateral hypothalamic area; NTS, nucleus of the solitary tract; PVN, paraventricular nucleus; PeV, periventricular nucleus; SON, supraoptic nucleus; VLM, ventrolateral medulla; ZI, zona incerta.

Fig. 2

High-resolution confocal microscopy of a single gastric cell co-expressing ghrelin (green) and NUCB2/nesfatin-1 (red) in separate cytoplasmic vesicles within the same cell. Confocal microscopy was performed using an x 100 objective and digital zoom, eight images in z-axis (stack size 24 × 24 × 7 μm) with dual laser excitation at 488 and 543 nm. Images were collected in two optical channels and photomultiplier tubes using FITC and TRITC filter sets, de-convoluted, and reconstructed into a three-dimensional image. Scale bar represents 1 μm. Reproduced with permission from reference [15]; Copyright 2009, The Endocrine Society.