title: Pediatric obesity and vitamin D deficiency: a proteomic approach identifies multimeric adiponectin as a key link between these conditions.
abstract: 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.
authors.affiliation: Laboratory of Clinical Pediatrics, Department of Health Sciences, Università del Piemonte Orientale "Amedeo Avogadro", Novara, Italy.
authors.forename: Gillian E
authors.initials: GE
authors.lastname: Walker
authors.affiliation: Division of Pediatrics, Department of Health Sciences, Università del Piemonte Orientale "Amedeo Avogadro", Novara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricotti
authors.affiliation: Laboratory of Clinical Pediatrics, Department of Health Sciences, Università del Piemonte Orientale "Amedeo Avogadro", Novara, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Roccio
authors.affiliation: Laboratory of Clinical Pediatrics, Department of Health Sciences, Università del Piemonte Orientale "Amedeo Avogadro", Novara, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Moia
authors.affiliation: Division of Pediatrics, Department of Health Sciences, Università del Piemonte Orientale "Amedeo Avogadro", Novara, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bellone
authors.affiliation: Division of Pediatrics, Department of Health Sciences, Università del Piemonte Orientale "Amedeo Avogadro", Novara, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Prodam
authors.affiliation: Division of Pediatrics, Department of Health Sciences, Università del Piemonte Orientale "Amedeo Avogadro", Novara, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Bona
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D052242:Adiponectin / Q000737:chemistry / Q000378:metabolism*; D000293:Adolescent; D000818:Animals; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D002762:Cholecalciferol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D063766:Pediatric Obesity / Q000378:metabolism*; D055503:Protein Multimerization; D040901:Proteomics / Q000379:methods; D014808:Vitamin D Deficiency / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D002762:Cholecalciferol