Uroguanylin: a new actor in the energy balance movie

Abstract

Uroguanylin (UGN) is a potential target in the fight against obesity. The mature protein is released after enzymatic cleavage from its natural precursor, proUGN. UGN is mostly produced in the gut, and its production is regulated by nutritional status. However, UGN is also produced in other tissues such as the kidneys. In the past, UGN has been widely studied as a natriuretic peptide owing to its involvement in several different pathologies such as heart failure, cancer and gastrointestinal diseases. However, recent studies have suggested that UGN also acts as a regulator of body weight homeostasis because it modulates both food intake and energy expenditure. This ultimately results in a decrease in body weight. This action is mediated by the sympathetic nervous system. Future studies should be directed at the potential effects of UGN agonists in regulating body weight in human obesity.

Circulating Pro-Uroguanylin Levels In Children And Their Relation To Obesity, Sex And Puberty

“…The increased pro-UGN levels found in boys with obesity are in agreement with data found in experimental animals, which showed higher UGN levels in diet-induced obese male mice 16 , but data comparing UGN in male and female rodents are not yet available. Nevertheless, the pro-satiety role of UGN in rodents (and completely unknown in humans) is still under discussion 7 , 13 – 15 , 24 , the scenario of higher pro-UGN levels in boys with obesity and its correlation with BMI may also suggest the existence of UGN resistance at least in children with obesity. It would be also interesting to study whether the sexual dimorphism of UGN is maintained in adults because other hormones deeply involved in energy balance, such as leptin, have shown different results in children and adults.…”

Mutational landscape of receptor guanylyl cyclase C: Functional analysis and disease‐related mutations

“…In PMV, GC‐C is mostly produced by neurons expressing anorexigenic leptin receptors (LepR), whereas in the VTA/SN, GC‐C is seen in neurons expressing tyrosine hydroxylase. After ingestion of food, prouroguanylin is secreted into the circulation, 62–64 and is processed into mature uroguanylin by hypothalamus 65 . This would result in activation of GC‐C and the increased accumulation of cGMP results in proopiomelanocortin and c‐Fos expression, which imparts the sense of satiety and reduces feeding 66 …”

Uroguanylin Improves Leptin Responsiveness in Diet-Induced Obese Mice

“…The key role of UGN in the regulation of energy homeostasis through the gut-brain axis has lately acquired great relevance [4,5,32]. In humans, UGN stimulates lipolysis in adipocytes [32] and the UGN mRNA expression is increased in obese patients following bariatric surgery [9].…”

“…Uroguanylin (UGN) has been recently proposed to be one of the members of this gut-brain axis implicated in body weight regulation [2,3,4,5,6]. UGN is a 16 amino-acid peptide secreted by the duodenal epithelial cells under its precursor form – prouroguanylin (pro-UGN) –, the pro-UGN is cleaved to give rise to the active form of the peptide which will bind the transmembrane receptor guanylin cyclase 2C (GUCY2C) [7].…”