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

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.

Reversal of Increase in Intestinal Permeability by Mangifera indica Seed Kernel Extract in High-Fat Diet-Induced Obese Mice

“…We also measured the expression levels of Nesfatin-1, a potent anti-obesity and anti-inflammatory peptide, in the jejunum. Nesfatin-1, an 82 amino acid peptide hormone derived from post-translational processing of the N-terminal of NUCB-2, is a potent anorexigenic hormone and reduces appetite and weight gain in both mice and humans [ 36 , 37 ]. Nesfatin-1 is expressed in several peripheral organs such as the liver, stomach, kidney, lungs, small intestine, large intestine, and the heart [ 36 , 37 , 38 ].…”

“…Nesfatin-1, an 82 amino acid peptide hormone derived from post-translational processing of the N-terminal of NUCB-2, is a potent anorexigenic hormone and reduces appetite and weight gain in both mice and humans [ 36 , 37 ]. Nesfatin-1 is expressed in several peripheral organs such as the liver, stomach, kidney, lungs, small intestine, large intestine, and the heart [ 36 , 37 , 38 ]. It has been demonstrated that HFD reduced serum levels of Nesfatin-1 in male C57BL/6J mice [ 39 ].…”

Sex‐specific association of plasma nesfatin‐1 concentrations with obesity in children

“…Studies analyzing these issues in adults and children have yielded contradictory results . Although nesfatin‐1 levels have been negatively correlated with BMI in healthy normal‐weight males, most of the studies in adults analyzing the relationship between nesfatin‐1 concentrations and BMI or presence of obesity have been performed in populations with different pathologies, such as patients with morbid obesity with type 2 diabetes mellitus or subjects with anorexia .…”

“…In humans, different analyses of the association of nesfatin‐1 with obesity have yielded divergent results. While some studies have reported negative correlations between nesfatin‐1 levels and obesity or body mass index (BMI) in adults and children, some have failed to find any correlation and others have reported a positive relationship between nesfatin‐1 concentrations and weight status in adults and childhood …”

Nucleobindin 2/nesfatin‐1 expression and colocalisation with neuropeptide Y and cocaine‐ and amphetamine‐regulated transcript in the human brainstem

“…In humans and rodents, immunohistochemical studies show that NUCB2/nesfatin‐1 is expressed in several hypothalamic nuclei 8,9,14‐16 . In rodents, in addition to the hypothalamus, NUCB2/nesfatin‐1 localisation has been described in a multitude of brainstem areas, such as the locus coeruleus (LC), the dorsal vagal complex (DVC), comprising the Sol, the 10N and the area postrema, as well as the raphe nuclei and the reticular formation 14,15,17,18 .…”