Garcés María F, Poveda Natalia E, Sanchez Elizabeth, Sánchez Ángel Y, Bravo Susana B, Vázquez María J, Diéguez Carlos, Nogueiras Rubén, Caminos Jorge E
Department of Physiology, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia.
Department of Pathology, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia.
Physiol Behav. 2014 Jun 22;133:216-22. doi: 10.1016/j.physbeh.2014.05.042. Epub 2014 Jun 4.
Nesfatin-1 is an anorexigenic neuropeptide derived by post-translational cleavage from the N-terminus region DNA binding/EF-hand/acidic amino acid rich region (NEFA)/nucleobindin2 (NucB2) protein through proteolytic prohormone convertases. This neuropeptide was originally localized in different appetite controlling areas such as the hypothalamic paraventricular nucleus, arcuate nucleus, supraoptic nucleus, lateral hypothalamic area, and nucleus tractus solitarius. The objective of this study was to determine the expression and the changes that occur to mRNA and protein of NucB2 and Nesfatin-1 serum levels during gestation. This study utilized molecular and immunological approaches to investigate the expression and regulation of NucB2/Nesfatin-1 protein throughout gestation in rat fed under ad libitum and food restricted conditions (30% nutrient restriction). NucB2 was immunolocalized in the amnion and decidua of the rat placenta. Nesfatin-1 serum levels were measured by radioimmunoassay on gestational days 12, 16, 19 and 21, showing a significant (p<0.01) decrease in serum levels after day 12 until the end of gestation in rats fed ad libitum. These results were correlated with the analysis of NucB2 mRNA, with a significant (p<0.01) reduction observed in both the mRNA and protein of NucB2 during the gestational days 12, 16 and 21. It was also observed that food restriction decreases Nesfatin-1 serum levels and NucB2 placental expression at day 16 of gestation when compared to pregnant rats fed ad libitum. This study illustrates for the first time through molecular and immunological approaches the NucB2 expression and regulation on rat placenta and that this peptide is regulated throughout pregnancy. Consistent with previous reports, our results provide additional evidence supporting the role of NucB2 protein as an anorexigenic peptide that may contribute to the regulation of feeding behavior and energy homeostasis. NucB2/Nesfatin-1 might play an important metabolic role during pregnancy and fetal development and its energy balance mediating role should be studied in various physiological and pathological conditions throughout gestation.
Nesfatin-1是一种厌食性神经肽，通过蛋白水解激素原转化酶从N端区域DNA结合/EF手型/富含酸性氨基酸区域（NEFA）/核结合蛋白2（NucB2）蛋白经翻译后切割产生。这种神经肽最初定位于不同的食欲控制区域，如下丘脑室旁核、弓状核、视上核、下丘脑外侧区和孤束核。本研究的目的是确定妊娠期间NucB2的mRNA和蛋白质表达以及Nesfatin-1血清水平的变化。本研究采用分子和免疫学方法，研究在自由采食和食物限制条件（30%营养限制）下喂养的大鼠整个妊娠期NucB2/Nesfatin-1蛋白的表达和调控。NucB2免疫定位在大鼠胎盘的羊膜和蜕膜中。在妊娠第12、16、19和21天通过放射免疫分析法测定Nesfatin-1血清水平，结果显示自由采食的大鼠在第12天后直至妊娠末期血清水平显著（p<0.01）下降。这些结果与NucB2 mRNA的分析相关，在妊娠第12、16和21天观察到NucB2的mRNA和蛋白质均显著（p<0.01）减少。还观察到，与自由采食的妊娠大鼠相比，食物限制在妊娠第16天降低了Nesfatin-1血清水平和NucB2胎盘表达。本研究首次通过分子和免疫学方法阐明了大鼠胎盘上NucB2的表达和调控，并且这种肽在整个妊娠期间受到调节。与先前的报道一致，我们的结果提供了额外的证据，支持NucB2蛋白作为一种厌食性肽的作用，它可能有助于调节摄食行为和能量稳态。NucB2/Nesfatin-1可能在妊娠和胎儿发育过程中发挥重要的代谢作用，其能量平衡调节作用应在整个妊娠期间的各种生理和病理条件下进行研究。
