Abstract
ContextLeptin secreted from adipose tissue signals peripheral energy status to the brain. Monogenic leptin deficiency results in severe early onset obesity with hyperphagia. Recently, a similar phenotype of inactivating leptin mutations but with preserved immunoreactivity and hence normal circulating immunoreactive leptin has been reported.ObjectiveWe aimed to evaluate the proportion of bioactive leptin serum levels (compared to immunoreactive leptin) as a biomarker for the screening of leptin gene mutations causing monogenic obesity. Furthermore, we aimed to compare the immunoreactive and bioactive leptin levels associations with parameters of insulin resistance and insulin secretion in obese children and adolescents.Patients and methodsWe measured bioactive and immunoreactive leptin levels by enzyme-linked immunosorbent assays in fasting serum samples of 70 children with severe (BMI SDS >3) non-syndromic obesity with onset <3 years of life from our Leipzig childhood obesity cohort (n = 1204). Sanger sequencing of the leptin gene was performed in probands with proportion of bioactive/immunoreactive leptin <90%.ResultsThe mean levels of bioactive and immunoreactive leptin were almost identical (41.1±25.2 vs. 41.1±25.4ng/mL). In three probands with the lowest bioactive leptin proportion (<90%) we did not identify mutations in the leptin gene. Compared to immunoreactive leptin, bioactive leptin showed similar and slightly better statistical associations with indices of insulin resistance in correlation and multivariate analyses.ConclusionIn our sample selected for severe early onset childhood obesity, we did not identify leptin gene mutations leading to decreased proportion of bioactive leptin.Nevertheless, the bioactive leptin levels were stronger associated with selected insulin secretion/resistance indices than the immunoreactive leptin levels.
Highlights
Leptin is a circulatingcytokine produced mainly by adipose tissue and acts as a satiety signal after binding to its receptor in the hypothalamus [1]
In our sample selected for severe early onset childhood obesity, we did not identify leptin gene mutations leading to decreased proportion of bioactive leptin
The bioactive leptin levels were stronger associated with selected insulin secretion/resistance indices than the immunoreactive leptin levels
Summary
Leptin is a circulating (adipo)cytokine produced mainly by adipose tissue and acts as a satiety signal after binding to its receptor in the hypothalamus [1]. Only rare monogenic cases of leptin deficiency due to the biallelic nonsynonymous mutations of the leptin gene with almost undetectable circulating leptin levels have been identified [4]. These patients had an early onset of severe obesity, hyperphagia and pubertal delay [4]. Two children with early onset massive obesity due to biallelic missense mutations of the leptin gene leading to formation of leptin with impaired functional activity but preserved immunoreactivity and normal leptin levels have been identified [5, 6]. It may be worthwhile to screen patients with severe early onset obesity for leptin insufficiency and to subject them to pharmacologic treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
