Pérez-Montarelo Dafne, Fernández Almudena, Barragán Carmen, Noguera Jose L, Folch Josep M, Rodríguez M Carmen, Ovilo Cristina, Silió Luis, Fernández Ana I
Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain.
PLoS One. 2013 Jun 18;8(6):e66398. doi: 10.1371/journal.pone.0066398. Print 2013.
The leptin (LEP) and its receptor (LEPR) regulate food intake and energy balance through hypothalamic signaling. However, the LEP-LEPR axis seems to be more complex and its expression regulation has not been well described. In pigs, LEP and LEPR genes have been widely studied due to their relevance. Previous studies reported significant effects of SNPs located in both genes on growth and fatness traits. The aim of this study was to determine the expression profiles of LEP and LEPR across hypothalamic, adipose, hepatic and muscle tissues in Iberian x Landrace backcrossed pigs and to analyze the effects of gene variants on transcript abundance. To our knowledge, non porcine LEPR isoforms have been described rather than LEPRb. A short porcine LEPR isoform (LEPRa), that encodes a protein lacking the intracellular residues responsible of signal transduction, has been identified for the first time. The LEPRb isoform was only quantifiable in hypothalamus while LEPRa appeared widely expressed across tissues, but at higher levels in liver, suggesting that both isoforms would develop different roles. The unique LEP transcript showed expression in backfat and muscle. The effects of gene variants on transcript expression revealed interesting results. The LEPRc.1987C>T polymorphism showed opposite effects on LEPRb and LEPRa hypothalamic expression. In addition, one out of the 16 polymorphisms identified in the LEPR promoter region revealed high differential expression in hepatic LEPRa. These results suggest a LEPR isoform-specific regulation at tissue level. Conversely, non-differential expression of LEP conditional on the analyzed polymorphisms could be detected, indicating that its regulation is likely affected by other mechanisms rather than gene sequence variants. The present study has allowed a transcriptional characterization of LEP and LEPR isoforms on a range of tissues. Their expression patterns seem to indicate that both molecules develop peripheral roles apart from their known hypothalamic signal transduction function.
瘦素（LEP）及其受体（LEPR）通过下丘脑信号传导调节食物摄入和能量平衡。然而，LEP-LEPR轴似乎更为复杂，其表达调控尚未得到充分描述。在猪中，由于LEP和LEPR基因的相关性，它们已被广泛研究。先前的研究报道了位于这两个基因中的单核苷酸多态性（SNP）对生长和脂肪性状有显著影响。本研究的目的是确定伊比利亚猪与长白猪回交后代中LEP和LEPR在下丘脑、脂肪、肝脏和肌肉组织中的表达谱，并分析基因变异对转录本丰度的影响。据我们所知，除了LEPRb之外，尚未描述非猪源的LEPR亚型。首次鉴定出一种短的猪LEPR亚型（LEPRa），它编码一种缺乏负责信号转导的细胞内残基的蛋白质。LEPRb亚型仅在下丘脑中可定量，而LEPRa在各组织中广泛表达，但在肝脏中表达水平更高，这表明这两种亚型发挥着不同的作用。独特的LEP转录本在背膘和肌肉中表达。基因变异对转录本表达的影响揭示了有趣的结果。LEPR c.1987C>T多态性对LEPRb和LEPRa在下丘脑的表达有相反的影响。此外，在LEPR启动子区域鉴定出的16个多态性中，有一个在肝脏LEPRa中显示出高差异表达。这些结果表明在组织水平上存在LEPR亚型特异性调控。相反，在所分析的多态性条件下未检测到LEP的差异表达，这表明其调控可能受其他机制而非基因序列变异的影响。本研究对一系列组织中的LEP和LEPR亚型进行了转录特征分析。它们的表达模式似乎表明，这两种分子除了其已知的下丘脑信号转导功能外，还发挥着外周作用。
