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

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.

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

“…However, the effect of peripheral nesfatin-1 administration upon feeding behaviour has yielded mixed findings. Thus the role of peripheral and in particular gastric nesfatin-1 remains to be determined 77 . Nevertheless, nesfatin-1 still represents a potential therapeutic target to treat people with obesity in light of its beneficial metabolic effects when administered centrally and the finding that peripheral nesfatin-1 can cross the blood brain barrier.…”

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

“…Feeding behavior is centrally orchestrated by complex neuronal networks residing in the hypothalamus, forebrain, and caudal brainstem, via multiple orexigenic and anorexigenic regulatory molecules [1, 2]. Nesfatin-1, a potent anorexigenic 82-amino acid peptide, is derived from the precursor nucleobindin-2 (NUCB2), a 396-amino acid protein synthesized both in the central nervous system and peripheral tissues [3, 4]. In rodents, NUCB2/nesfatin-1 is highly expressed in the appetite-control hypothalamic nuclei, including the paraventricular (PVN), supraoptic (SON), arcuate (Arc), and lateral hypothalamic area (LHA).…”

“…Although NUCB2/nesfatin-1 cognate receptor has yet to be identified, animal model studies have provided evidence for the important physiological role of NUCB2/nesfatin-1 in energy homeostasis [4]. Central administration of an antibody neutralizing nesfatin-1 enhanced appetite, and injection of a NUCB2 antisense oligonucleotide increased food intake and body weight, thus indicating that both endogenous NUCB2 and nesfatin-1 possess anorexigenic and anti-obesogenic properties [3, 4].…”

“…Central administration of an antibody neutralizing nesfatin-1 enhanced appetite, and injection of a NUCB2 antisense oligonucleotide increased food intake and body weight, thus indicating that both endogenous NUCB2 and nesfatin-1 possess anorexigenic and anti-obesogenic properties [3, 4]. Moreover, NUCB2/nesfatin-1 injected peripherally, intracerebroventricularly, or microinjected directly into hypothalamic nuclei, such as PVN, Arc, or LHA, in animal models, reduced food intake and body weight and decreased gastric motility/secretions, via a leptin-independent and oxytocin/melanocortin-dependent pathway [3, 20-30].…”

Effects of endurance training and herb supplementation on tissue nesfatin-1/nucleobindin-2 and ghrelin mRNA expression

“…In addition to nesfatin-1 gene expression in different tissues, the presence of nesfatine-1 in different biological fluids such as human breast milk, salvia, serum/plasma, cerebrospinal fluid [9,[16][17][18]. Although the action of nesfatin-1 on food intake behavior and body weight get much more attention , but on the basis of published data nesfatin-1 could act as a biomarkers and also has an anti-hyperglycemic, anti-inflammatory, neuroendocrine regulator, and lowering body fat via appetite suppression, and metabolic and cardiovascular actions [9,[19][20][21][22][23].The levels of tissue and plasma nesfatin-1 could be affected under nutritional status (fasting and fed states, restraint stress abdominal surgery, high fat diets, , , glycemic state, different nutrient manipulation [9,24,25]. In contrast to the nesfatin-1 whose recognized and discovered as an anorexigenic peptide, ghrelin is discovered in peripheral tissue (fundus part of stomach) and introduced as an orexigenic peptide, but according to the several published studies this peptide also centrally expresses [26][27][28].…”