Abstract

Nucleobindin-1 has high sequence similarity to nucleobindin-2, which encodes the anorectic and metabolic peptide, nesfatin-1. We previously reported a nesfatin-1-like peptide (NLP), anorectic in fish and insulinotropic in mice islet beta-like cells. The main objective of this research was to determine whether NLP is a metabolic regulator in male Wistar rats. A single intraperitoneal (IP) injection of NLP (100 μg/kg BW) decreased food intake and increased ambulatory movement, without causing any change in total activity or energy expenditure when compared to saline-treated rats. Continuous subcutaneous infusion of NLP (100 μg/kg BW) using osmotic mini-pumps for 7 days caused a reduction in food intake on days 3 and 4. Similarly, water intake was also reduced for two days (days 3 and 4) with the effect being observed during the dark phase. This was accompanied by an increased RER and energy expenditure. However, decreased whole-body fat oxidation, and total activity were observed during the long-term treatment (7 days). Body weight gain was not significantly different between control and NLP infused rats. The expression of mRNAs encoding adiponectin, resistin, ghrelin, cholecystokinin and uncoupling protein 1 (UCP1) were significantly upregulated, while leptin and peptide YY mRNA expression was downregulated in NLP-treated rats. These findings indicate that administration of NLP at 100 μg/kg BW reduces food intake and modulates whole body energy balance. In summary, NLP is a novel metabolic peptide in rats.

Highlights

  • Nucleobindin 1 (NUCB1) is a widely expressed multi-domain calcium and DNA binding protein [1] that exhibits significant structural homology with a related protein, nucleobindin 2 (NUCB2)

  • We found that nesfatin-1-like peptide (NLP) alters the expression of mRNAs encoding key hormones involved in the regulation of food intake and energy balance

  • Our objective was to determine whether NLP modulates feeding and metabolism at a dose identical to the concentration of nesfatin-1 that was found metabolically active in rats

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Summary

Introduction

Nucleobindin 1 (NUCB1) is a widely expressed multi-domain calcium and DNA binding protein [1] that exhibits significant structural homology with a related protein, nucleobindin 2 (NUCB2). NUCB1 is expressed in the pituitary, thyroid, parathyroid, gastrointestinal tract, adrenals, gonads and pancreatic islets of langerhans. KG received a postdoctoral research fellowship from the SHRF. NR is a recipient of college of graduate and postdoctoral studies (CGPS) Dean’s scholarship from the University of Saskatchewan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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