Background: CREB-regulated transcription coactivator 3 (CRTC3) is found in adipocytes where it may promote obesity through disruption of catecholamine signaling. CRTC3 knockout mice are resistant to diet-induced obesity.
Objective and Hypotheses: The goals of the present study were i) to assess whether CRTC3 is a soluble protein secreted by adipose tissue ii) to explore whether CRTC3 is detectable and quantifiable in the circulation, and iii) to ascertain whether CRTC3 concentrations may be related to metabolic markers in children.
Method: Explants of visceral and subcutaneous adipose tissue from 12 prepubertal children were cultured to study the secretion of CRTC3 by adipose tissue using immunoblot and ELISA. We also performed a cross-sectional and longitudinal study in asymptomatic prepubertal Caucasian children to assess the presence of CRTC3 in the circulation and to study the associations between serum CRTC3 and metabolic markers, namely BMI, waist circumference, systolic blood pressure (SBP) and HMW-adiponectin, cross-sectionally in 211 children at age 7 years (52% girls; 19% overweight subjects) and longitudinally in 115 children from the same sample at age ~10 years.
Results: Measurable concentrations of CRTC3 were found in conditioned media of adipose tissue biopsies and in serum samples from the study subjects. In the cross-sectional study, higher CRTC3 concentrations were associated with higher BMI (P=0.001), waist (P=0.003), SBP (P=0.007), and lower HMW adiponectin (P=0.003). In the longitudinal study, serum concentrations of CRTC3 at age ~7 years were associated with changes in BMISDS (β=0.327; P=0.001; R2=0.114) and in HMW adiponectin (β=−0.271; P=0.014; R2=0.101) at age ~10 years.
Conclusions: In prepubertal children, CRTC3 is present in the circulation, partly as a result of adipose tissue secretion. Higher serum CRTC3 concentrations are related and predict a poorer metabolic profile. We herein suggest that CRTC3 is a new adipokine related to childhood obesity.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology