The Tissue Distribution of Nesfatin-1/NUCB2 in Mouse

Abstract

Nesfatin-1, an anorexic nucleobindin-2 (NUCB2)-derived hypothalamic peptide, controls appetite and energy metabolism. Recent studies show that nesfatin-1/NUCB2 is expressed not only in the brain but also in gastric and adipose tissues. Thus, we investigated the distributions of nesfatin-1/NUCB2 in various tissues of male and female mice by real-time PCR, western blotting, and immunohistochemical staining. Real-time PCR analyses showed that NUCB2 mRNA was predominantly expressed in the pituitary and at lower levels in the hypothalamus, spleen, thymus, heart, liver, and muscle of both male and female mice. Expression was much higher in reproductive organs, such as the testis, epididymis, ovary, and uterus, than in the hypothalamus. Western blot analysis of the nesfatin-1 protein level showed similar results to the real-time PCR analyses in both male and female mice. These results suggest that nesfatin-1/NUCB2 have widespread physiological effects in endocrine and non-endocrine organs. In addition, immunohistochemical staining revealed that nesfatin-1 was localized in interstitial cells, including Leydig cells and in the columnar epithelium of the epididymis. Nesfatin-1 was also expressed in theca cells and interstitial cells in the ovary and in epithelial cells of the endometrium and uterine glands in the uterus. These results suggest that nesfatin-1 is a novel potent regulator of steroidogenesis and gonadal function in male and female reproductive organs. Further studies are required to elucidate the functions of nesfatin-1 in various organs of male and female mice.

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

“…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). It is extensively colocalized with neuropeptides involved in the regulation of hunger, satiety, and other homeostatic functions, such as oxytocin, vasopressin, melanin-concentrating hormone (MCH), and cocaine- and amphetamine-regulated transcript (CART) [3, 5-10]. In the periphery, NUCB2/nesfatin-1 has been detected in gastric mucosa, adipose tissue, pancreatic islets, and testes as well as in cerebrospinal fluid and plasma in animals and humans [9-19].…”

“…Several animal studies have demonstrated NUCB2/nesfatin-1 distribution in hypothalamic nuclei and brain areas with established roles in energy homeostasis, neuroendocrine functions, and body weight regulation [3, 5-10, 33]. However, NUCB2/nesfatin-1 protein expression in the human hypothalamus remains to be identified.…”

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

“…pancreas and testis (Gonzalez et al 2009, Shimizu et al 2009b, Ramanjaneya et al 2010, Kim et al 2014. Within the central nervous system (CNS), Nucb2 mRNA is present, for example, in the hypothalamus and brainstem (Oh-I et al 2006, Brailoiu et al 2007) (for more details we refer to the respective sections).…”

“…Alternatively, other enzymes, for example, the cell surface membrane-bound protein furin, which cleaves at the same general motif as the PCs, might be involved in NUCB2 processing (Seidah & Prat 2002). In most rodent tissues studied, for example, gastric mucosa, pancreas, pituitary gland and testis, either only the precursor NUCB2 or indistinguishable NUCB2/nesfatin-1 was detected , Kim et al 2014. However, nesfatin-1, the amino terminal putative cleavage product of NUCB2, was unambiguously identified in the hypothalamus and CSF of rodents (Oh-I et al 2006) and also in human plasma (Tsuchiya et al 2010).…”

“…Only in some studies, western blots were performed to distinguish between NUCB2 and nesfatin-1 based on the molecular weight (e.g. Stengel et al 2009b, Kim et al 2014. Throughout this review, the term 'NUCB2/nesfatin-1' is used whenever one or the other was not positively identified.…”