Grupo Fisiopatología Endocrina, Laboratorio 14, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Universidad de Santiago de Compostela (USC), Travesía da Choupana s/n, 15706, Santiago de Compostela, Spain.
CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Universidad de Santiago de Compostela (USC), Santiago de Compostela, Spain.
Eur J Nutr. 2016 Mar;55(2):529-536. doi: 10.1007/s00394-015-0869-2. Epub 2015 Mar 6.
Uroguanylin (UGN) is a 16 amino acid peptide produced mainly by intestinal epithelial cells. Nutrients intake increases circulating levels of prouroguanylin that is processed and converted to UGN to activate the guanylyl cyclase 2C receptor (GUCY2C). Given that the UGN-GUCY2C system has been proposed as a novel gut-brain endocrine axis regulating energy balance, the aim of the present study was to investigate the regulation of UGN protein levels in duodenum and circulating levels in lean and obese mice under different nutritional conditions and its potential interaction with leptin.
Swiss, C57BL/6 wild-type and ob/ob male adult mice under different nutritional conditions were used: fed ad libitum standard diet (control); 48 h fasting (fasted); 48 h fasting followed by 24 h of feeding (refed); and fed high-fat diet (45 %) during 10 weeks. In addition, peripheral leptin administration was performed. Intestinal uroguanylin expression was studied by Western blot analysis; plasma levels were measured by ELISA.
Food deprivation significantly reduced plasma UGN levels, which were correlated with the lower protein levels of UGN in duodenum. These effects were reverted after refeeding and leptin challenge. Consistently, in ob/ob mice UGN expression was decreased, whereas leptin treatment up-regulated UGN levels in duodenum in these genetically modified mice compared to WT. Diet-induced obese mice displayed increased UGN levels in intestine and plasma in comparison with lean mice.
Our findings suggest that UGN levels are correlated with energy balance status and that the regulation of UGN by nutritional status is leptin-dependent.
尿鸟苷素（UGN）是一种由肠道上皮细胞产生的 16 个氨基酸肽。营养物质的摄入会增加循环中前尿鸟苷素的水平，其被加工并转化为 UGN，以激活鸟苷酸环化酶 2C 受体（GUCY2C）。鉴于 UGN-GUCY2C 系统被提议作为一种新的肠道-大脑内分泌轴来调节能量平衡，本研究旨在研究不同营养条件下瘦鼠和肥胖鼠十二指肠 UGN 蛋白水平和循环水平的调节及其与瘦素的潜在相互作用。
使用不同营养条件下的瑞士、C57BL/6 野生型和 ob/ob 雄性成年小鼠：自由喂食标准饮食（对照）；48 小时禁食（禁食）；48 小时禁食后 24 小时喂食（再喂食）；10 周内喂食高脂肪饮食（45%）。此外，还进行了外周性瘦素给药。通过 Western blot 分析研究肠道尿鸟苷素表达；通过 ELISA 测量血浆水平。
食物剥夺显著降低了血浆 UGN 水平，这与十二指肠 UGN 蛋白水平降低相关。这些影响在再喂食和瘦素挑战后得到逆转。一致地，ob/ob 小鼠中 UGN 表达降低，而与 WT 相比，瘦素治疗上调了这些基因修饰小鼠十二指肠中的 UGN 水平。与瘦鼠相比，饮食诱导肥胖鼠的肠道和血浆 UGN 水平升高。
我们的发现表明 UGN 水平与能量平衡状态相关，并且营养状态对 UGN 的调节依赖于瘦素。
