Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway

Cell Metab. 2009 Nov;10(5):355-65. doi: 10.1016/j.cmet.2009.09.002.


The hypothalamic paraventricular nucleus (PVN) functions as a center to integrate various neuronal activities for regulating feeding behavior. Nesfatin-1, a recently discovered anorectic molecule, is localized in the PVN. However, the anorectic neural pathway of nesfatin-1 remains unknown. Here we show that central injection of nesfatin-1 activates the PVN and brain stem nucleus tractus solitarius (NTS). In the PVN, nesfatin-1 targets both magnocellular and parvocellular oxytocin neurons and nesfatin-1 neurons themselves and stimulates oxytocin release. Immunoelectron micrographs reveal nesfatin-1 specifically in the secretory vesicles of PVN neurons, and immunoneutralization against endogenous nesfatin-1 suppresses oxytocin release in the PVN, suggesting paracrine/autocrine actions of nesfatin-1. Nesfatin-1-induced anorexia is abolished by an oxytocin receptor antagonist. Moreover, oxytocin terminals are closely associated with and oxytocin activates pro-opiomelanocortin neurons in the NTS. Oxytocin induces melanocortin-dependent anorexia in leptin-resistant Zucker-fatty rats. The present results reveal the nesfatin-1-operative oxytocinergic signaling in the PVN that triggers leptin-independent melanocortin-mediated anorexia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anorexia / metabolism
  • Autocrine Communication
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Leptin / metabolism
  • Melanocortins / metabolism*
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Neuroendocrine Cells / metabolism
  • Nucleobindins
  • Oxytocin / metabolism*
  • Paracrine Communication
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Pro-Opiomelanocortin / metabolism*
  • Rats
  • Rats, Zucker
  • Signal Transduction / physiology*
  • Solitary Nucleus / metabolism*


  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Leptin
  • Melanocortins
  • Nerve Tissue Proteins
  • Nucb1 protein, mouse
  • Nucb1 protein, rat
  • Nucleobindins
  • Oxytocin
  • Pro-Opiomelanocortin