Abstract

Nesfatin-1 (Nesf-1) was identified as an anorexigenic and well conserved molecule in rodents and fish. While tissue distribution of NUCB2 (Nucleobindin 2)/Nesf-1 is discretely known in vertebrates, reports on ontogenetic expression are scarce. Here, we examine the age-related central and peripheral expression of NUCB2/Nesf-1 in the teleost African turquoise killifish Nothobranchius furzeri, a consolidated model organism for aging research. We focused our analysis on brain areas responsible for the regulation of food intake and the rostral intestinal bulb, which is analogous of the mammalian stomach. We hypothesize that in our model, the stomach equivalent structure is the main source of NUCB2 mRNA, displaying higher expression levels than those observed in the brain, mainly during aging. Remarkably, its expression significantly increased in the rostral intestinal bulb compared to the brain, which is likely due to the typical anorexia of aging. When analyzing the pattern of expression, we confirmed the distribution in diencephalic areas involved in food intake regulation at all age stages. Interestingly, in the rostral bulb, NUCB2 mRNA was localized in the lining epithelium of young and old animals, while Nesf-1 immunoreactive cells were distributed in the submucosae. Taken together, our results represent a useful basis for gaining deeper knowledge regarding the mechanisms that regulate food intake during vertebrate aging.

Highlights

  • Nucleobindin (NUCB) belongs to the family of calcium and DNA binding proteins and comprises two members, NUCB1 and NUCB2

  • Due to the third round of whole-genome duplication in teleost, two paralogues are present in the genome of N. furzeri: NUCB2A and NUCB2B

  • Sequences were obtained from the Nothobranchius furzeri Genome Browser–NFINgb: accession number was Nfu_g_1_003870 for NUCB2A and Nfu_g_1_018131 for NUCB2B [34]

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Summary

Introduction

Nucleobindin (NUCB) belongs to the family of calcium and DNA binding proteins and comprises two members, NUCB1 and NUCB2. Hypothalamic neurons which co-expressed Nesf-1, antidiuretic hormone (ADH), corticotropin (CRH), and thyrotropin-releasing hormone (TRH) constitute an important network which regulates food intake. This network acts through the anorexigenic system of the melanocortin above all. Expression levels of NUCB2/Nesf-1 in purified small endocrine cells of gastric mucosa have been reported to be 10-fold higher compared to brain levels [11] Based on these indications, the stomach is considered one of the main sources of circulating NUCB2/Nesf-1 [12], supporting the hypothesis that NUCB2 is cleaved and Nesf-1 is produced at the gastric level [13]

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