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

Folgueira, Cintia; Barja-Fernández, Silvia; González-Sáenz, Patricia; Castelao, Cecilia; Vázquez-Cobela, Rocío; Pena-León, Verónica; Ruíz‐Piñón, Manuel; Casanueva, Felipe F.; Diéguez, Carlos; Leis, Rosaura; Nogueiras, Rubén; Seoane, Luísa M.

doi:10.1038/s41598-018-32767-7

Cited by 7 publications

(4 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although there is no direct evidence in the literature regarding the effects of linaclotide on energy homeostasis, recent reports have indicated that the activation of its receptor Gucy2c is involved in the control of food intake [3] and EE [7] in rodents. Moreover, in humans circulating levels of proUGN are altered in obese adult subjects [8] and children [20]. The fact that oral linaclotide acts through the central nervous systems targeting BAT thermogenesis and EE without affecting feeding behavior is similar to our previous findings in which a central infusion of UGN was able to induce the same effects [7].…”

Section: Discussionsupporting

confidence: 86%

Oral Pharmacological Activation of Hypothalamic Guanylate Cyclase 2C Receptor Stimulates Brown Fat Thermogenesis to Reduce Body Weight

et al. 2020

Self Cite

View full text Add to dashboard Cite

Linaclotide is a synthetic peptide approved by the FDA for the treatment of constipation-predominant irritable bowel syndrome and chronic constipation. Linaclotide binds and activates the transmembrane receptor guanylate cyclase 2C (Gucy2c). Uroguanylin (UGN) is a 16 amino acid peptide that is mainly secreted by enterochromaffin cells in the duodenum and proximal small intestine. UGN is the endogenous ligand of Gucy2c and decreases body weight in diet-induced obese (DIO) mice via the activation of the thermogenic program in brown adipose tissue. Therefore, we wanted to evaluate whether oral linaclotide could also improve DIO mice metabolic phenotype. In this study, we have demonstrated that DIO mice orally treated with linaclotide exhibited a significant reduction of body weight without modifying food intake. Linaclotide exerts its actions through the central nervous system, and more specifically, via Gucy2c receptors located in the mediobasal hypothalamus, leading to the activation of the sympathetic nervous system to trigger the thermogenic activity of brown fat stimulating energy expenditure. These findings indicate for first time that, in addition to its effects at intestinal level C.F. and F.L.T.-L. contributed equally to this work.

show abstract

Section: Discussionsupporting

confidence: 86%

Oral Pharmacological Activation of Hypothalamic Guanylate Cyclase 2C Receptor Stimulates Brown Fat Thermogenesis to Reduce Body Weight

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…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 …”

Section: Extra‐intestinal Roles Of Gc‐cmentioning

confidence: 99%

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

2020

View full text Add to dashboard Cite

Guanylyl cyclase C (GC-C) is the receptor for the heat-stable enterotoxin, which causes diarrhea, and the endogenous ligands, guanylin and uroguanylin. GC-C is predominantly expressed in the intestinal epithelium and regulates fluid and ion secretion in the gut. The receptor has a complex domain organization, and in the absence of structural information, mutational analysis provides clues to mechanisms of regulation of this protein. Here, we review the mutational landscape of this receptor that reveals regulatory features critical for its activity. We also summarize the available information on mutations in GC-C that have been reported in humans and contribute to severe gastrointestinal abnormalities. Since GC-C is also expressed in extraintestinal tissues, it is likely that mutations thus far reported in humans may also affect other organ systems, warranting a close observation of these patients in future. K E Y W O R D ScGMP, guanylyl cyclase C, human mutation, meconium ileus, secretory diarrhea

show abstract

“…One study reported a negative correlation between plasma fasting prouroguanylin concentration and BMI in girls, but a positive correlation in boys (40). Another study found female but not male adolescents with obesity had lower prouroguanylin concentrations (19).…”

Section: Discussionmentioning

confidence: 99%

Postprandial regulation of prouroguanylin in humans of a healthy weight and those who are overweight or with obesity

et al. 2020

View full text Add to dashboard Cite

Uroguanylin is a peptide gut hormone proposed to have a role in signalling post meal satiety. Uroguanylin circulates as its pro-hormone, prouroguanylin. There has been limited investigation of the regulation of prouroguanylin by food; therefore we investigated prouroguanylin regulation following meals. In separate experiments we investigated the effects of high calorie (1451 kcal) and medium calorie (725 kcal), high fat meals, on plasma prouroguanylin concentrations. We then examined the effect of a 722.5 kcal high carbohydrate breakfast on prouroguanylin concentrations, comparing the response in healthy weight adults versus those who are overweight/ with obesity. The 1451 kcal meal increased prouroguanylin concentrations, versus fasting at 60 (P<0.05), 90 (P<0.01) and 120 (P<0.001) minutes. After the 725 kcal meal hormone concentrations rose more slowly and were significant versus fasting concentrations at 120 minutes (P<0.01). The high carbohydrate breakfast 722.5 kcal, led to an initial suppression of hormone concentrations at 30 mins post meal (P<0.05) followed by an increase in concentrations until they were significant versus fasting at 120 mins (P<0.01). Participants overweight/ with obesity had lower fasting prouroguanylin concentrations (P<0.05), but post meal concentrations did not differ between the groups. Our results suggest there is a delayed increase in prouroguanylin concentrations following, large and regular sized mixed macronutrient meals rich in fat or carbohydrate. Fasting levels are suppressed in people who are overweight/ with obesity, but the post meal response remains intact. There may be potential to target post meal release of prouroguanylin in obesity.

show abstract

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

Cited by 7 publications

References 30 publications

Oral Pharmacological Activation of Hypothalamic Guanylate Cyclase 2C Receptor Stimulates Brown Fat Thermogenesis to Reduce Body Weight

Oral Pharmacological Activation of Hypothalamic Guanylate Cyclase 2C Receptor Stimulates Brown Fat Thermogenesis to Reduce Body Weight

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

Postprandial regulation of prouroguanylin in humans of a healthy weight and those who are overweight or with obesity

Contact Info

Product

Resources

About