Rajeswari Jithine Jayakumar, Unniappan Suraj
Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Department of Biological Sciences, University of Calgary, 507 Campus Dr NW, Calgary, AB T2N 4V8, Canada.
Animals (Basel). 2023 Apr 22;13(9):1437. doi: 10.3390/ani13091437.
Nesfatin-1 and nesfatin-1-like peptide (Nlp) are derived from precursors nucleobindin-2 and -1, two calcium and DNA binding proteins, respectively. Both peptides exhibit hormone-like actions in mammals and fish. These functions include insulinotropic effects of nesfatin-1 and Nlp seen in mice and their growth hormone suppressive actions reported in goldfish. We hypothesized that nesfatin-1 and Nlp are insulin stimulatory (in adipose tissue) and modulate growth hormone and insulin-like growth factors and glucose transporters in goldfish. To test this, goldfish were intraperitoneally injected with either nesfatin-1 or Nlp (50 ng/g BW) or saline alone (control) and sampled at one-hour post-injection (in vivo study). In a separate study, tissue samples were collected and were incubated with either nesfatin-1 or Nlp for one or six hours (in vitro study). Transcript (mRNA) abundance data from the adipose tissue suggest that both nesfatin-1 and Nlp significantly upregulate the abundance of preproinsulin, insulin receptors, and and mRNAs. Meanwhile, the abundance of preproglucagon mRNA in the adipose tissue was significantly downregulated in both in vivo and in vitro studies. These results agree with the insulinotropic and glucagonostatic roles for nesfatin-1 and Nlp reported in rodents. The transcript abundance of growth regulators (, , and ) and glucose transporters ( and ) were upregulated in the muscle, while an opposite effect on these mRNAs was found in the liver of goldfish following nesfatin-1 and Nlp administration. Our results suggest that both nesfatin-1 and Nlp have tissue-specific regulatory roles on growth and glucoregulatory elements in the liver and muscle of goldfish. This agrees with our previous studies that showed a suppressive action of nesfatin-1 on growth hormone in goldfish liver. The results presented here provide strong supportive/confirmatory evidence for tissue-specific insulinotropic and gluco- and growth-regulatory actions of nesfatin-1 and Nlp in goldfish.
Nesfatin-1和nesfatin-1样肽（Nlp）分别来源于前体核结合蛋白-2和-1，这两种蛋白分别是钙结合蛋白和DNA结合蛋白。这两种肽在哺乳动物和鱼类中均表现出类似激素的作用。这些功能包括在小鼠中观察到的nesfatin-1和Nlp的促胰岛素作用以及在金鱼中报道的它们的生长激素抑制作用。我们推测nesfatin-1和Nlp具有刺激胰岛素分泌（在脂肪组织中）的作用，并能调节金鱼体内的生长激素、胰岛素样生长因子和葡萄糖转运蛋白。为了验证这一点，给金鱼腹腔注射nesfatin-1或Nlp（50 ng/g体重）或单独注射生理盐水（对照组），并在注射后1小时取样（体内研究）。在另一项研究中，收集组织样本并与nesfatin-1或Nlp孵育1小时或6小时（体外研究）。来自脂肪组织的转录本（mRNA）丰度数据表明，nesfatin-1和Nlp均显著上调胰岛素原、胰岛素受体以及 和 mRNA的丰度。同时，在体内和体外研究中，脂肪组织中胰高血糖素原mRNA的丰度均显著下调。这些结果与啮齿动物中报道的nesfatin-1和Nlp的促胰岛素和抑制胰高血糖素分泌的作用一致。nesfatin-1和Nlp给药后，金鱼肌肉中生长调节因子（ 、 和 ）和葡萄糖转运蛋白（ 和 ）的转录本丰度上调，而在金鱼肝脏中则发现这些mRNA有相反的变化。我们的结果表明，nesfatin-1和Nlp对金鱼肝脏和肌肉中的生长和糖调节元件具有组织特异性调节作用。这与我们之前的研究结果一致，即nesfatin-1对金鱼肝脏中的生长激素有抑制作用。此处呈现的结果为nesfatin-1和Nlp在金鱼中具有组织特异性的促胰岛素以及糖和生长调节作用提供了有力的支持/证实性证据。
