OR15-6 Circulating Dickkopf-1 Protein Levels in Lean and Obese Children: Evidence of Involvement of Wnt Signaling

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR15-Adipokine Action
Basic/Clinical
Sunday, June 16, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 12:30 PM
Room 303 (Moscone Center)
Ioannis Papassotiriou*1, Evangelos Terpos2, Christina Kanaka-Gantenbein2 and George P. Chrousos2
1Agia Sophia Children's Hospital, Athens, Greece, 2University of Athens School of Medicine, 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 six hours after onset of human adipogenesis and this is followed by an increase in DKK-1 protein. With further differentiation, mRNA and protein levels of DKK-1 progressively decline to undetectable in mature adipocytes. The transient induction of DKK-1 correlates with down-regulation of cytoplasmic and nuclear beta-catenin levels, representing a surrogate marker of canonical Wnt signaling and Wnt/beta-catenin transcriptional activity1. 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: a) DKK-1 levels were significantly higher in lean girls than obese girls 37.5±18.0 vs. 18.6±2.4 pg/mL, p=0.009, b) 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), c) logDKK-1 values correlated significantly only with adiponectin levels (r=-0.404, p=0.008), d) DKK-1 and RANKL levels correlated positively with each other, (r=0.492, p<0.001) and e) hs-CRP and DKK-1 levels correlated, negatively with each other (r=-0.371, p=0.01).

Conclusions: 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.

1Marinou et al. Trends Endocrinol Metab. 23: 628-636, 2012.  

Nothing to Disclose: IP, ET, CK, GPC

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