Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2017 May 23;12(5):e0178107. doi: 10.1371/journal.pone.0178107. eCollection 2017.

Concordance of bioactive vs. total immunoreactive serum leptin levels in children with severe early onset obesity.

Author information

Center for Pediatric Research Leipzig, University Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany.
First Department of Pediatrics, Medical Faculty at the Comenius University, Bratislava, Slovakia.
DIABGENE Laboratory, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany.
Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Leipzig, Germany.
CrescNet, University of Leipzig, Leipzig, Germany.



Leptin 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.


We 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.


We 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%.


The 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.


In 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.

PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center