Abstract
A recently discovered satiety molecule, nesfatin-1, is localized in neurons of the hypothalamus and brain stem and colocalized with stress-related substances, corticotropin-releasing hormone (CRH), oxytocin, proopiomelanocortin, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). Intracerebroventricular (icv) administration of nesfatin-1 produces fear-related behaviors and potentiates stressor-induced increases in plasma adrenocorticotropic hormone (ACTH) and corticosterone levels in rats. These findings suggest a link between nesfatin-1 and stress. In the present study, we aimed to further clarify the neuronal network by which nesfatin-1 could induce stress responses in rats. Restraint stress induced c-Fos expressions in nesfatin-1-immunoreactive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus, and in the nucleus of solitary tract (NTS), locus coeruleus (LC) and dorsal raphe nucleus (DR) in the brain stem, without altering plasma nesfatin-1 levels. Icv nesfatin-1 induced c-Fos expressions in the PVN, SON, NTS, LC, DR and median raphe nucleus, including PVN-CRH, NTS-NA, LC-NA and DR-5-HT neurons. Nesfatin-1 increased cytosolic Ca2+ concentration in the CRH-immunoreactive neurons isolated from PVN. Icv nesfatin-1 increased plasma ACTH and corticosterone levels. These results indicate that the central nesfatin-1 system is stimulated by stress and activates CRH, NA and 5-HT neurons and hypothalamic-pituitary-adrenal axis, evoking both central and peripheral stress responses.
Highlights
Nesfatin-1 is processed by cleavage of a precursor, NEFA/nucleobindin2 (NUCB2), and is distributed in the central nervous system (CNS) implicated in the regulation of feeding, including the hypothalamic paraventricular nucleus (PVN), arcuate nucleus (ARC), lateral hypothalamic area and supraoptic nucleus (SON) [1]
This study aimed to clarify whether the central nesfatin1 system and/or the plasma nesfatin-1 level is activated by restraint stress, to specify the central areas and neuron species targeted by stress and icv nesfatin-1, and to examine whether icv nesfatin-1 stimulates HPA axis in rats. c-Fos protein expression was examined to detect neuronal activation
The present study has demonstrated that the central nesfatin-1 system but not the plasma nesfatin-1 level is activated by restraint stress and that icv nesfatin-1 activates corticotropin-releasing hormone (CRH), noradrenaline and 5-HT neurons and increases plasma adrenocorticotropic hormone (ACTH) and glucocorticoid levels
Summary
Nesfatin-1 is processed by cleavage of a precursor, NEFA/nucleobindin (NUCB2), and is distributed in the central nervous system (CNS) implicated in the regulation of feeding, including the hypothalamic paraventricular nucleus (PVN), arcuate nucleus (ARC), lateral hypothalamic area and supraoptic nucleus (SON) [1]. Nesfatin-1 and oxytocin both suppresses food intake in Zucker-fatty rats with mutated leptin receptor, and leptin-induced satiety is unaltered by immunoneutralizing nesfatin-1 IgG [1,6]. These results suggest that nesfatin-1 induces anorexia in a leptin-independent and melanocortin-dependent manner [1,6]. The CRH and melanocortin [10] pathways are implicated in stress
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
