Nucleobindin-2/Nesfatin-1 in the Human Hypothalamus Is Reduced in Obese Subjects and Colocalizes with Oxytocin, Vasopressin, Melanin-Concentrating Hormone, and Cocaine- and Amphetamine-Regulated Transcript

Neuroendocrinology. 2019;108(3):190-200. doi: 10.1159/000496731. Epub 2019 Jan 9.

Abstract

Background/aims: Nesfatin-1, processed from nucleobindin-2 (NUCB2), is a potent anorexigenic peptide being expressed in rodent hypothalamic nuclei and involved in the regulation of feeding behavior and body weight in animals. The present study aimed to investigate NUCB2/nesfatin-1 protein expression in the human hypothalamus as well as its correlation with body weight.

Methods: Sections of hypothalamus and adjacent cholinergic basal forebrain nuclei, including the nucleus basalis of Meynert (NBM) and the diagonal band of Broca (DBB), from 25 autopsy cases (17 males, 8 females; 8 lean, 9 overweight, 8 obese) were examined using immunohistochemistry and double immunofluorescence labeling.

Results: Prominent NUCB2/nesfatin-1 immunoexpression was detected in supraoptic, paraventricular, and infundibular nuclei, lateral hypothalamic area (LHA)/perifornical region, and NBM/DBB. NUCB2/nesfatin-1 was found to extensively colocalize with (a) oxytocin and vasopressin in paraventricular and supraoptic nuclei, (b) melanin-concentrating hormone in the LHA, and (c) cocaine- and amphetamine-regulated transcript in infundibular and paraventricular nuclei and LHA. Interestingly, in the LHA, NUCB2/nesfatin-1 protein expression was significantly decreased in obese, compared with lean (p < 0.01) and overweight (p < 0.05) subjects.

Conclusions: The findings of the present study are suggestive of a potential role for NUCB2/nesfatin-1 as an integral regulator of food intake and energy homeostasis in the human hypothalamus. In the LHA, an appetite- and reward-related brain area, reduced NUCB2/nesfatin-1 immunoexpression may contribute to dysregulation of homeostatic and/or hedonic feeding behavior and obesity. NUCB2/nesfatin-1 localization in NBM/DBB might imply its participation in the neuronal circuitry controlling cognitive influences on food intake and give impetus towards unraveling additional biological actions of NUCB2/nesfatin-1 in human neuronal networks.

Keywords: Cocaine- and amphetamine-regulated transcript; Food intake; Hypothalamic nuclei; Lateral hypothalamic area; Melanin-concentrating hormone; Nesfatin-1; Nucleobindin-2; Obesity; Oxytocin; Vasopressin.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Body Weight
  • Case-Control Studies
  • Female
  • Humans
  • Hypothalamic Hormones / metabolism*
  • Hypothalamus / metabolism*
  • Male
  • Melanins / metabolism*
  • Middle Aged
  • Nerve Tissue Proteins / metabolism*
  • Nucleobindins / biosynthesis*
  • Obesity / metabolism*
  • Oxytocin / metabolism*
  • Pituitary Hormones / metabolism*
  • Vasopressins / metabolism*

Substances

  • Hypothalamic Hormones
  • Melanins
  • NUCB2 protein, human
  • Nerve Tissue Proteins
  • Nucleobindins
  • Pituitary Hormones
  • cocaine- and amphetamine-regulated transcript protein
  • Vasopressins
  • Oxytocin
  • melanin-concentrating hormone