Nesfatin-1: functions and physiology of a novel regulatory peptide

J Endocrinol. 2017 Jan;232(1):R45-R65. doi: 10.1530/JOE-16-0361. Epub 2016 Oct 17.

Abstract

Nesfatin-1 was identified in 2006 as a potent anorexigenic peptide involved in the regulation of homeostatic feeding. It is processed from the precursor-peptide NEFA/nucleobindin 2 (NUCB2), which is expressed both in the central nervous system as well as in the periphery, from where it can access the brain via non-saturable transmembrane diffusion. In hypothalamus and brainstem, nesfatin-1 recruits the oxytocin, the melancortin and other systems to relay its anorexigenic properties. NUCB2/nesfatin-1 peptide expression in reward-related areas suggests that nesfatin-1 might also be involved in hedonic feeding. Besides its initially discovered anorexigenic properties, over the last years, other important functions of nesfatin-1 have been discovered, many of them related to energy homeostasis, e.g. energy expenditure and glucose homeostasis. Nesfatin-1 is not only affecting these physiological processes but also the alterations of the metabolic state (e.g. fat mass, glycemic state) have an impact on the synthesis and release of NUCB2 and/or nesfatin-1. Furthermore, nesfatin-1 exerts pleiotropic actions at the level of cardiovascular and digestive systems, as well as plays a role in stress response, behavior, sleep and reproduction. Despite the recent advances in nesfatin-1 research, a putative receptor has not been identified and furthermore potentially distinct functions of nesfatin-1 and its precursor NUCB2 have not been dissected yet. To tackle these open questions will be the major objectives of future research to broaden our knowledge on NUCB2/nesfatin-1.

Keywords: NUCB2; cardiovascular; energy homeostasis; glucose metabolism; nesfatin-1.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium-Binding Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Energy Metabolism / physiology*
  • Glucose / metabolism*
  • Homeostasis / physiology
  • Humans
  • Hypothalamus / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Nucleobindins
  • Signal Transduction / physiology*

Substances

  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • NUCB2 protein, human
  • Nerve Tissue Proteins
  • Nucleobindins
  • Glucose