Di Guglielmo Matthew D, Tonb Dalal, He Zhaoping, Adeyemi Adebowale, van Golen Kenneth L
Department of Pediatrics.
Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington.
J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):489-495. doi: 10.1097/MPG.0000000000001796.
Disruption of satiety signaling may lead to increased caloric intake and obesity. Uroguanylin, the intestinal hormone, travels as a precursor to the central nervous system where it activates guanylyl cyclase C and stimulates pro-satiety neurons. Rodent studies have demonstrated that guanylyl cyclase C-knockout mice overeat and have increased weight gain versus wild-type mice and hyper-caloric obesity diminishes uroguanylin expression. We measured circulating plasma pro-uroguanylin, along with other gastrointestinal peptides and inflammatory markers, in human adolescents with and without obesity, as a pilot study. We hypothesized that adolescents with obesity would have less circulating pro-uroguanylin than adolescents without obesity have.
We recruited 24 adolescents (age 14-17 years) with and without obesity (body mass index >95% or body mass index <95%) and measured plasma pro-uroguanylin at fasting and successive time points after a meal. We measured 3 other satiety hormones and 2 inflammatory markers to characterize overall satiety signaling and highlight any link between uroguanylin and inflammation.
Female adolescents with obesity had lower circulating pro-uroguanylin levels than female adolescents without obesity; we observed no difference in males. Other measured gastrointestinal peptides varied in their differences between cohorts. Inflammatory markers were higher in female participants with obesity.
In adolescents with and without obesity, we can measure circulating pro-uroguanylin levels. In female adolescents without obesity, levels are particularly higher. Pro-uroguanylin secretion patterns differ from other circulating gastrointestinal peptides. In female adolescents with obesity, inflammation correlates with decreased pro-uroguanylin levels.
饱腹感信号的破坏可能导致热量摄入增加和肥胖。尿鸟苷素作为一种肠道激素，以前体形式进入中枢神经系统，在那里它激活鸟苷酸环化酶C并刺激促饱腹感神经元。啮齿动物研究表明，与野生型小鼠相比，鸟苷酸环化酶C基因敲除小鼠食量过大且体重增加更多，高热量肥胖会使尿鸟苷素表达减少。作为一项初步研究，我们测量了有肥胖和无肥胖的青少年的循环血浆前尿鸟苷素，以及其他胃肠道肽和炎症标志物。我们假设肥胖青少年的循环前尿鸟苷素水平低于无肥胖青少年。
我们招募了24名年龄在14 - 17岁之间的有肥胖和无肥胖（体重指数>95%或体重指数<95%）的青少年，并在空腹及餐后连续时间点测量血浆前尿鸟苷素。我们测量了其他3种饱腹感激素和2种炎症标志物，以表征整体饱腹感信号，并突出尿鸟苷素与炎症之间的任何联系。
肥胖女性青少年的循环前尿鸟苷素水平低于无肥胖的女性青少年；我们在男性中未观察到差异。其他测量的胃肠道肽在不同队列之间的差异各不相同。肥胖女性参与者的炎症标志物水平较高。
在有肥胖和无肥胖的青少年中，我们可以测量循环前尿鸟苷素水平。在无肥胖的女性青少年中，水平尤其更高。前尿鸟苷素的分泌模式与其他循环胃肠道肽不同。在肥胖女性青少年中，炎症与前尿鸟苷素水平降低相关。
