ESPE Abstracts (2014) 82 FC12.5

Low Circulating Levels of DKK-1 Protein in Obese Children Indicate Suppression of Canonical Wnt Signaling

Christina Kanaka-Gantenbeina, Evangelos Terposb, George Chrousosa & Ioannis Papassotiriouc

aFirst Department of Pediatrics, University of Athens School of Medicine, Athens, Greece; bDepartment of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece; cDepartment of Clinical Biochemistry, ‘Aghia Sophia’ Children’s Hospital, Athens, Greece

Background: Secretion of Wnt-proteins by adipose cells plays an important role in the control of adipogenesis. The Wnt-antagonist, dickkopf-1 (DKK-1), is secreted by human pre-adipocytes and influences adipocyte maturation and growth. DKK-1 mRNA increases 6 h after onset of human adipogenesis followed by an increase in DKK-1 protein. Of note, DKK-1 protein has been implicated also in bone remodeling pathways.

Patients and Methods: In this study we measured the circulating DKK-1 levels in 16 lean and 25 obese girls using immunoenzymatic techniques and we investigated possible correlations of DKK-1 levels with parameters of anthropometric evaluation; insulin resistance; adipose tissue secretory molecules (adiponectin, leptin, retinol-binding-protein-4 (RBP-4) and lipocalin-2); bone remodeling biomarkers (osteoprotegerin (OPG), receptor-activator of NF-κB ligand (RANKL), osteocalcin, C-terminal-cross-linking telopeptide of collagen type-I (CTX), bone-alkaline-phosphatase (bALP) and tartrate-resistant-acid- phosphatase-isoform-5b (bone-TRACP-5b) and a low grade inflammation marker (hs-CRP)).

Results: We found that: i) DKK-1 levels were significantly higher in lean than obese girls 37.5±18.0 vs 18.6±2.4 pg/ml, P=0.009, ii) BMI and HOMA index values correlated negatively with DKK-1 levels (r=−0.508, P<0.001 and r=−0.380, P<0.01, respectively), iii) logDKK-1 values correlated significantly only with adiponectin levels (r=−0.404, P=0.008), iv) DKK-1 and RANKL levels correlated positively with each other, (r=0.492, P<0.001) and v) hs-CRP and DKK-1 levels correlated, negatively with each other (r=−0.371, P=0.01).

Conclusion: Our preliminary findings suggest that indices of metabolic syndrome such as obesity, insulin resistance, low adiponectin and low grade inflammation are negatively associated with circulating DKK-1 protein levels in children. Obesity is characterized by inappropriate expansion of adipose cells (hypertrophic obesity) and is caused by an inability to recruit and differentiate new precursor cells. Thus, the impairment of adipogenesis observed in obesity appears to be due mainly to suppression of canonical Wnt signaling via induction of DKK-1. The latter might connect obesity with increased osteoclastogenesis.

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