Tissue-Specific Localization NUCB2/nesfatin-1 in the Liver and Heart of Mouse Fetus

Abstract

NUCB2/nesfatin-1 is first known to be expressed in the hypothalamus while controlling appetite and energy metabolism. However, recent studies have shown that NUCB2/nesfatin-1 was expressed in the various organs as well as the hypothalamus. Our previous reports also demonstrated that NUCB2/nesfatin-1 was expressed in the ovary, testis, pituitary gland, lung, kidney, and stomach of fetal and adult mice. However, the role of NUCB2/nesfatin-1 in mouse fetus remains unknown. Thus, the aim of this study was to investigate whether NUCB2/nestatin-1 is expressed in mouse fetus at the developmental stage in which organogenesis begins. To do this, we performed in situ hybridization (ISH) and immunohistochemistry (IHC) staining to examine the distribution of NUCB2 mRNA and nesfatin-1 protein in the mouse fetal organs during early developmental stages, especially at embryonic day (E) 10.5. As a result of ISH, NUCB2 mRNA positive signals were more frequent in the liver, but there were relatively few positive signals in heart. On the other hand, no positive signals were detected in other organs. These ISH results were validated by IHC staining and qRT-PCR analysis. Expression of nesfatin-1 protein detected by IHC staining was similar to that of NUCB2 mRNA detected by ISH in the liver and heart. In addition, the levels of NUCB2 mRNA expression analyzed by qRT-PCR were significantly increased in the liver and heart compared to other organs of the mouse fetus at E13.5, whereas its level was extensively decreased in the liver, but increased in the lung, stomach, and kidney of the mouse fetus at E17.5. These results suggest that NUCB2/nesfatin-1 may play an important role in liver and heart development and physiological functions in the developmental process of mouse fetus. Further studies are needed on the function of NUCB2/nesfatin-1, which is highly expressed in the various organs, including liver and heart during mouse development.

Nucleobindin-2 consists of two structural components: The Zn2+-sensitive N-terminal half, consisting of nesfatin-1 and -2, and the Ca2+-sensitive C-terminal half, consisting of nesfatin-3

“…Nucb2 also participates in other biological processes, e.g., adipogenesis [39] , biomineralization [40] and carcinogenesis [41] , [42] . Additionally, Nucb2 is ubiquitously expressed in the central nervous system [38] and peripheral tissues, such as the digestive tract [43] , reproductive system [44] , pancreas [45] , [46] , and heart [47] . The multifunctionality of Nucb2 may result from its structure.…”

Nesfatin-1 and nesfatin-1-like peptide attenuate hepatocyte lipid accumulation and nucleobindin-1 disruption modulates lipid metabolic pathways

“…NUCB2/NESF-1-like immunoreactivity was observed in cytoplasmic vesicles of cells in peripheral tissues, including gastric cells 29 and rat Leydig cells 30 . NUCB1 mRNA and nesfatin-1 immunoreactivity was reported in embryonic and adult mouse liver, suggesting a local role for these peptides 31 . NUCB1 and NUCB2 mRNA and their proteins were upregulated in NESF-1- and NLP-treated HepG2/C3A cells, respectively.…”

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

“…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 ].…”