Pediatric Obesity and Vitamin D Deficiency: A Proteomic Approach Identifies Multimeric Adiponectin as a Key Link between These Conditions

• Published in: PloS one Vol. 9; no. 1; p. e83685
• Main Authors: Walker, Gillian E., Ricotti, Roberta, Roccio, Marta, Moia, Stefania, Bellone, Simonetta, Prodam, Flavia, Bona, Gianni
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.01.2014; Public Library of Science (PLoS)
• Subjects: 3T3-L1 Cells; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adiponectin; Adiponectin - chemistry; Adiponectin - metabolism; Adolescent; Adults; Analysis; Animals; Avogadro, Amedeo (1776-1856); Biology; Biomarkers; Blood pressure; Blood proteins; Body fat; Body mass index; Child; Child health; Child, Preschool; Childhood obesity; Children; Cholecalciferol - therapeutic use; Diabetes; Diabetes mellitus; Endoplasmic reticulum; Female; Gels; Gene expression; Health sciences; Humans; Insulin; Insulin resistance; Laboratories; Liver diseases; Male; Medicine; Metabolic syndrome; Metabolites; Mice; Molecular weight; Nutrition research; Obesity; Pediatric Obesity - metabolism; Pediatrics; Pharmacology; Protein Multimerization; Proteomics - methods; Spots; Studies; Supplementation; Supplements; Teenagers; Two dimensional analysis; Vitamin D; Vitamin D Deficiency - drug therapy; Vitamin D Deficiency - metabolism; Vitamin D3; Vitamin deficiency; Weight control
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0083685

Key circulating molecules that link vitamin D (VD) to pediatric obesity and its co-morbidities remain unclear. Using a proteomic approach, our objective was to identify key molecules in obese children dichotomized according to 25OH-vitamin D (25OHD) levels. A total of 42 obese children (M/F = 18/24) were divided according to their 25OHD3 levels into 25OHD3 deficient (VDD; n = 18; 25OHD<15 ng/ml) or normal subjects (NVD; n = 24; >30 ng/ml). Plasma proteomic analyses by two dimensional (2D)-electrophoresis were performed at baseline in all subjects. VDD subjects underwent a 12mo treatment with 3000 IU vitamin D3 once a week to confirm the proteomic analyses. The proteomic analyses identified 53 "spots" that differed between VDD and NVD (p<0.05), amongst which adiponectin was identified. Adiponectin was selected for confirmational studies due to its tight association with obesity and diabetes mellitus. Western Immunoblot (WIB) analyses of 2D-gels demonstrated a downregulation of adiponectin in VDD subjects, which was confirmed in the plasma from VDD with respect to NVD subjects (p<0.035) and increased following 12mo vitamin D3 supplementation in VDD subjects (p<0.02). High molecular weight (HMW) adiponectin, a surrogate indicator of insulin sensitivity, was significantly lower in VDD subjects (p<0.02) and improved with vitamin D3 supplementation (p<0.042). A direct effect in vitro of 1α,25-(OH)2D3 on adipocyte adiponectin synthesis was demonstrated, with adiponectin and its multimeric forms upregulated, even at low pharmacological doses (10(-9) M) of 1α,25-(OH)2D3. This upregulation was paralleled by the adiponectin interactive protein, DsbA-L, suggesting that the VD regulation of adiponectin involves post-transciptional events. Using a proteomic approach, multimeric adiponectin has been identified as a key plasma protein that links VDD to pediatric obesity.