Pilot Study Measuring the Novel Satiety Hormone, Pro‐Uroguanylin, in Adolescents With and Without Obesity

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.