Background: Rodent models of leptin inactivity show progressive obesity due to exaggerated food intake. In humans, only rare monogenic cases of leptin deficiency and almost absent circulating leptin levels have been identified. Recently, two cases of children with early onset massive obesity due to biofunctionally inactive leptin in the face of normal total levels have been identified.
Objective and hypotheses: Here we aimed to identify leptin inactivity in obese children through decreased proportion of bioactive leptin.
Method: Seventy probands with severe early-onset non-syndromic obesity (age of obesity onset <3 years and BMI SDS >3 SDS at the age of 14 years) were selected from a large Leipzig childhood obesity cohort (n=1377) for the leptin measurement. Serum concentrations of whole and bioactive leptin were measured with enzyme-linked immunosorbent assays. Proportion of bioactive leptin was evaluated as percentage from the whole leptin levels. Sanger sequencing of the leptin gene was performed in probands with proportion of bioleptin <90%.
Results: In 70 selected probands the mean levels of bioactive and whole leptin were 37.4±24.1 ng/ml, and 32.0±20.6 ng/ml, respectively. The corresponding proportion of bioactive leptin was 122.3±26.2% (47.5188.3%). We identified five probands suspicious for impaired leptin activity (bioactive leptin <90%). However, DNA analysis of the leptin gene did not confirm causal mutations.
Conclusion: In our sample selected for severe early onset childhood obesity, we did not identify leptin gene mutations leading to decreased proportion of bioactive leptin.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology