Endocrine Abstracts

Key circulating molecules that link the emerging role of vitamin-D to pediatric obesity and its co-morbidities remain unclear. To identify potentially involved regulators, this study analyzed plasma proteoma from obese children dichotomized by 25OH-vitamin D (25OHD) levels and upon vitamin-D3 therapy in 25OHD deficient subjects.

A total of 42 obese children (M/F=18/24, bmi>95° centile) were selected and divided according to 25OHD levels into deficient (G1; n=18; 25OHD<14.5 ng/ml) or normal 25OHD (G2; n=24; >30 ng/ml). Eight subjects from G1 underwent a 12mo treatment with 400 UI/die vitamin-D3. Proteomic analyses by 2D-electrophoresis with different IPG ranges were performed at baseline with spots quantitated by PDQuest.

2D-electrophoresis with IPG3-10 identified 28 spots significantly different between groups (P<0.05). Among these, 57% were localized within PI3-6. Analysis restricted to this range revealed 20 spots significantly different between groups (P<0.05). Overall, 20% of IPG3-6 associated spots were downregulated in G1 compared to G2. Adiponectin was selected for confirmational studies due to strong correlations with obesity and its co-morbidities, as well as its localization within a susceptibility gene loci. WIB analysis of 2D-gels showed downregulation of adiponectin in 25OHD-deficient subjects. Adiponectin expression was lower in plasma from G1 than G2 (7187±383 vs 8594±587 AU; P<0.035) and increased following 12mo vitamin-D3 treatment in 80% of G1 subjects by an average of 8% (P<0.02). Analysis of HMW adiponectin, a surrogate indicator of insulin sensitivity, demonstrated significantly lower levels in G1 subjects (697.1±127.7 vs 1270.5±198 AU; P=0.015), which improved upon vitamin-D3 therapy (583.3±162.1 vs 1412.1±251.7 AU; P<0.02).

Our proteomic approach to identify key circulating molecules that link 25OHD levels to pediatric obesity, has demonstrated that vitamin-D deficiency is associated with an altered adiponectin expression, specifically the HMW form, which can be significantly improved by vitamin-D3 administration. Direct effects of vitamin-D on adiponectin production in the adipose tissue remain to be elucidated.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.