Nephrology Research and Development Unit, Faculty of Medicine, University of Porto, Alameda Prof. Hernaˆ ni Monteiro, 4200–319 Porto, Portugal.
Exp Biol Med (Maywood). 2013 Jan;238(1):90-7. doi: 10.1258/ebm.2012.012232.
Guanylin (GN), uroguanylin (UGN) and the GC-C receptor have been associated with two endocrine axes: the salt and water homeostasis regulating enterorenal axis and the recently described appetite-regulating UGN/GC-C extraintestinal axis. The present work assessed the mRNA expression levels of GN peptides system (GPS) in a model of diet-induced obesity. Male C57BL/6J mice were submitted to either a high-fat high-simple carbohydrate diet (obese) or a normal diet (control). The renal and intestinal GN, UGN and GC-C receptor mRNA expression were evaluated by reverse transcriptase quantitative polymerase chain reaction in both groups, during normo-saline (NS) and high-saline (HS) diet. The diet-induced obesity was accompanied by glucose intolerance and insulin resistance as well as by a significant increase in blood pressure. During NS diet, obese mice presented reduced mRNA expression of GN in ileum and colon, UGN in duodenum, ileum and colon and GC-C in duodenum, jejunum, ileum and colon. This was accompanied by increased UGN mRNA expression in renal cortex. During HS diet, obese mice presented reduced mRNA expression of GN in jejunum as well as reduced mRNA expression of UGN and GC-C in duodenum, jejunum and colon. The data obtained suggest that, in a mouse model of diet-induced obesity, a down-regulation of intestinal mRNA expression of GN, UGN and its GC-C receptor is accompanied by a compensatory increase of renal UGN mRNA expression. We hypothesize that the decrease in gene expression levels of intestinal GPS may contribute to the development of hypertension and obesity during hypercaloric diet intake.
guanylin (GN)、uroguanylin (UGN) 和 GC-C 受体与两个内分泌轴有关：调节盐和水稳态的肠肾轴和最近描述的调节食欲的 UGN/GC-C 肠外轴。本工作评估了饮食诱导肥胖模型中 GN 肽系统 (GPS) 的 mRNA 表达水平。雄性 C57BL/6J 小鼠分别给予高脂肪高简单碳水化合物饮食（肥胖）或正常饮食（对照）。在正常盐（NS）和高盐（HS）饮食条件下，通过逆转录定量聚合酶链反应评估两组肾和肠 GN、UGN 和 GC-C 受体 mRNA 表达。饮食诱导的肥胖伴有葡萄糖不耐受和胰岛素抵抗，以及血压显著升高。在 NS 饮食期间，肥胖小鼠回肠和结肠中 GN、十二指肠、回肠和结肠中 UGN 以及十二指肠、空肠、回肠和结肠中 GC-C 的 mRNA 表达降低。这伴随着肾皮质 UGN mRNA 表达的增加。在 HS 饮食期间，肥胖小鼠空肠中 GN 的 mRNA 表达降低，以及十二指肠、空肠和结肠中 UGN 和 GC-C 的 mRNA 表达降低。所得数据表明，在饮食诱导肥胖的小鼠模型中，肠 GPS 的 mRNA 表达下调伴随着肾 UGN mRNA 表达的代偿性增加。我们假设肠道 GPS 基因表达水平的降低可能有助于高热量饮食摄入期间高血压和肥胖的发展。
