Relative leptin deficiency in children with severe early-onset obesity (SEOO) – results of the Early-onset Obesity and Leptin – German-Polish Study (EOL-GPS)

Agnieszka Zachurzok; Michael B. Ranke; Bertram Flehmig; Katarzyna Jakubek-Kipa; Katarzyna Marcinkiewicz; Artur Mazur; Elzbieta Petriczko; Lutz Pridzun; Julia von Schnurbein; Mieczyslaw Walczak; Ewa Malecka-Tendera; Martin Wabitsch; Stephanie Brandt

doi:10.1515/jpem-2019-0469

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Article

Relative leptin deficiency in children with severe early-onset obesity (SEOO) – results of the Early-onset Obesity and Leptin – German-Polish Study (EOL-GPS)

Agnieszka Zachurzok , Michael B. Ranke , Bertram Flehmig , Katarzyna Jakubek-Kipa , Katarzyna Marcinkiewicz , Artur Mazur , Elzbieta Petriczko , Lutz Pridzun , Julia von Schnurbein , Mieczyslaw Walczak , Ewa Malecka-Tendera , Martin Wabitsch and Stephanie Brandt

Published/Copyright: January 13, 2020

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 33 Issue 2

Abstract

Background

Severe early-onset obesity (SEOO) in children is a common feature of monogenic obesity. Gene defects of the leptin-melanocortin pathway can be analysed biochemically and genetically. The aim of this study was to search for children with leptin deficiency or biologically inactive leptin in a cohort of children with SEOO and to study associations between leptin parameters and anthropometric data.

Methods

The cohort included n = 50 children with SEOO (22 boys) who were recruited at one of four study centres (Germany: Ulm; Poland: Katowice, Szczecin, Rzeszow) between October 2015 and October 2017. Weight (kg) and height (m) were measured, Tanner stage was obtained and a fasting serum blood sample was taken. Serum levels of total leptin (LEP, ng/mL), biologically active leptin (bioLEP, ng/mL) and soluble leptin receptor (sLEPR, ng/mL) were measured. The body mass index (BMI [kg/m²]), BMI z-score (World Health Organization [WHO]), quotient of bioLEP/LEP and leptin-standard deviation score (LEP-SDS) (Tanner stage, BMI and sex-adjusted) were calculated.

Results

We did not find any child with leptin deficiency or biologically inactive leptin in our cohort. The serum LEP and bioLEP levels were strongly correlated with age (r = 0.50, p < 0.05) and BMI (r = 0.70; p < 0.0001). Girls had higher LEP and bioLEP levels (49.7 ± 35.9 vs. 37.1 ± 25.5 ng/mL, p > 0.05) as well as lower LEP-SDS than boys (−1.77 ± 2.61 vs. −1.40 ± 2.60, p > 0.05). sLEPR levels were negatively correlated with BMI values (r = −0.44; p < 0.05), LEP (r = −0.39; p < 0.05) and bioLEP levels (r = −0.37; p < 0.05). Interestingly, there was a strong inverse relationship between LEP-SDS and BMI (r = −0.72, p < 0.001).

Conclusions

In this cohort with SEOO, we identified no new cases of children with leptin deficiency or bioinactive leptin. A strong negative correlation between the LEP-SDS and BMI values could be interpreted as relative leptin deficiency in children with SEOO. In case this hypothesis can be confirmed, these children would benefit from a substitution therapy with methionyl human leptin (metreleptin™).

Keywords: children; leptin; severe early-onset obesity

Corresponding author: Dr. biol. hum. Stephanie Brandt, Center for Rare Endocrine Diseases, Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Eythstr. 24, 89075 Ulm, Germany, Phone: +49(0)73150057426

Acknowledgments

We thank all children and their parents for their participation in the EOL-GPS. We would also like to thank Mediagnost (www.mediagnost.de) for measuring leptin parameters in serum blood samples of the study participants.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: Slaski Uniwersytet Medyczny, Funder Id: http://dx.doi.org/10.13039/100007771, KNW-1-120/N/7/K.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2019-10-07

Accepted: 2019-11-18

Published Online: 2020-01-13

Published in Print: 2020-02-25

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Articles in the same Issue

https://doi.org/10.1515/jpem-2019-0469

Keywords for this article

children; leptin; severe early-onset obesity