Recent progress in research on the distribution and function of NUCB2/Nesfatin-1 in peripheral tissues [Review]

Abstract

Abstract. Nesfatin-1 is a polypeptide derived from the posttranslational processing of the N-terminal fragment of nucleobindin 2 (NUCB2), that was originally identified as an anorexigenic hypothalamic neuropeptide. A number of reports have recently shown that NUCB2/Nesfatin-1 is widely expressed in various peripheral tissues, including those of the gastrointestinal tract where it may participate in various pathophysiological processes. One of its roles may be regulation of energy homeostasis. As a result, Nesfatin-1 may be a novel target for exploring the underlying mechanisms and the treatment of metabolic syndromes.Key words: Nesfatin-1, Peripheral tissues, Satiety factor, Metabolic syndrome Along with the improvement in living standards, obesity-related metabolic syndrome, whose incidence is rapidly growing every year, negatively affects people's health and life. It was well known that obesity arose from an imbalance between energy intake and expenditure; however, certain mechanisms involved in this process were still unknown. In 2006 Oh I et al. [1] found that an intracerebroventricular injection of recombinant nucleobindin 2(NUCB2), later termed NUCB2-encoded satiety-and fat-influencing protein or Nesfatin, reduced nocturnal feeding and body weight gain. Subsequent studies found that intraperitoneal injection of Nesfatin-1 also suppressed food intake and decreased body weight gain [2]. These observations suggested that Nesfatin-1 played an important role in the regulation of body energy balance. It had been found that plasma Nesfatin-1 crossed the bloodbrain barrier without saturation [3], and either peripheral or central administration of Nesfatin-1 reduced food intake through a leptin-independent mechanism [4]. Therefore, research on the distribution and function of Nesfatin-1 in peripheral tissue were important. Herein, we provided a brief review of the current knowledge regarding Nesfatin-1 distribution and function in peripheral tissues. genomics and protein structure of nUCB2/nesfatin-1NUCB2 was originally identified as a hypothalamus secreted protein that was found in hypothalamic nuclei involved in feeding regulation. Furthermore, NUCB2 was composed of a signal peptide containing 24 amino acids and a protein structure containing 396 amino acids [5]. Its gene was located on the 11q151, and the aminoacid sequence of NUCB2 was highly conserved in rats (95% homology) and mice (87.4% homology) [6].Posttranslational processing of NUCB2 by prohormone convertase produces 3 cleavage products, namely Nesfatin-1 (1-82), . Nesfatin-1 is an 82-amino-acid peptide derived from posttranslational processing of the N-terminal fragment of NUCB2 and has a predicted molecular mass of 9.8 kDa. A study by Oh I et al. indicated that of the 3 cleavage products, only Nesfatin-1 can decrease food intake and body weight [1]. Furthermore, structural and functional analyses showed that after intraperitoneal and intracerebroventricular injection of the 3 segments of Nesfatin-1, the N-terminal segment, the C-terminal segment, or t...

High NUCB2 expression level represents an independent negative prognostic factor in Chinese cohorts of non-metastatic clear cell renal cell carcinoma patients

“…NUCB2/Nesfatin-1 showed widespread expression in the body, where it was mainly reported to participate in multiple pathophysiological processes like nocturnal feeding and body weight regulation [10]. Recently, a few studies revealed the correlation between NUCB2 and tumor development and possible mechanism.…”

“…NUCB2, as a precursor protein of nesfatin-1, was identified as a hypothalamus secreted protein originally and was found to be involved in feeding regulation in hypothalamic nuclei [10]. Subsequently, NUCB2 expression was found in peripheral tissues such as pancreatic islets, testis, stomach and adipose tissue [11, 12].…”

Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration

“…A number of studies subsequently demonstrated NUCB2 expression in peripheral tissues such as stomach, pancreatic islets, testis, and adipose tissues [10][11][12][13], and a wide variety of basic cellular functions of NUCB2 including insulin release, adipocyte differentiation and myocardial performance has been proposed (reviewed in Cao et al [14]). Recently, possible roles of NUCB2 have been proposed in several human malignancies, which to date remain controversial [15][16][17][18][19][20].…”

A novel function of NUCB2 in promoting the development and invasion of renal cell carcinoma

“…NUCB2 was first reported to be expressed in the arcuate nucleus, lateral hypothalamus, paraventricular nucleus and supraoptic nucleus of the hypothalamus (4,5). Following this, a number of studies have suggested that the primary peripheral source of NUCB2 was originated from stomach mucosa, and NUCB2 was also peripherally expressed in pancreas and fat tissues (7,8). In the hypothalamus, NUCB2 inhibits food intake and promotes body metabolism (4).…”