Anna Prats-Puig1, Pilar Soriano-Rodríguez2, Glòria Oliveras3, Gemma Carreras-Badosa4, Sílvia Espuña5, Ferran Díaz-Roldán4, Francis de Zegher6, Lourdes Ibáñez7, Judit Bassols4, Teresa Puig8, Abel López-Bermejo9. 1. Pediatrics Research Group, Girona Institute for Biomedical Research, Girona, Spain; Pediatrics, Dr. Josep Trueta Hospital, Girona, Spain; Department of Physical Therapy, EUSES University School, University of Girona, Girona, Spain; aprats@idibgi.org. 2. Clinical Laboratory Salut Empordà Foundation, Figueres, Spain; 3. New Therapeutic Targets Lab (TargetsLab), Unit of Oncology, University of Girona, Girona, Spain; Department of Pathology and Anatomical Sciences, Dr. Josep Trueta Hospital, Girona, Spain; 4. Pediatrics Research Group, Girona Institute for Biomedical Research, Girona, Spain; Pediatrics, Dr. Josep Trueta Hospital, Girona, Spain; 5. Pediatrics, Salut Empordà Foundation, Figueres, Spain; 6. Department of Development and Regeneration, University of Leuven, Leuven, Belgium; 7. Pediatric Endocrinology, Sant Joan de Déu Children's Hospital, Esplugues, Barcelona; CIBERDEM (Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders), Instituto de Salud Carlos III, Madrid, Spain; 8. New Therapeutic Targets Lab (TargetsLab), Unit of Oncology, University of Girona, Girona, Spain; 9. Pediatrics Research Group, Girona Institute for Biomedical Research, Girona, Spain; Pediatrics, Dr. Josep Trueta Hospital, Girona, Spain; TransLab Research Group, Department of Medical Sciences, Faculty of Medicine, University of Girona, Girona, Spain.
Abstract
BACKGROUND: CREB-regulated transcription coactivator 3 (CRTC3) is found in adipocytes, where it may promote obesity through disruption of catecholamine signaling. We wished to assess whether CRTC3 is a soluble protein secreted by adipose tissue, explore whether CRTC3 is detectable and quantifiable in the circulation, and ascertain whether CRTC3 serum concentrations are related to metabolic markers in children. METHODS: Explants of adipose tissue from 12 children were cultured to study adipocyte cell size and the secretion of CRTC3 (immunoblot and ELISA). We also performed a cross-sectional and longitudinal study in 211 asymptomatic prepubertal white children at age 7 years, 115 of whom were followed up at age approximately 10 years. We measured circulating concentrations of CRTC3 and studied associations between serum CRTC3 and metabolic markers. RESULTS: Measurable concentrations of CRTC3 were found in conditioned media of adipose tissue explants and in serum samples. CRTC3 concentrations in visceral adipose tissue were negatively associated with adipocyte cell size and positively related to adipocyte cell number (P < 0.05). In the cross-sectional study, higher CRTC3 concentrations were associated with higher body mass index (P = 0.001), waist circumference (P = 0.003), and systolic blood pressure (P = 0.007) and lower high molecular weight adiponectin (P = 0.003). In the longitudinal study, serum concentrations of CRTC3 at age approximately 7 years were associated with changes in waist circumference (β = 0.254; P = 0.004; r = 0.145) and high molecular weight adiponectin (β=-0.271; P = 0.014; r = 0.101), respectively, at age approximately 10 years. CONCLUSIONS: CRTC3, a newly identified protein that is related to childhood obesity, is present in the circulation, partly as a result of adipose tissue secretion. Higher serum CRTC3 concentrations are related to and predict a poorer metabolic profile in children.
BACKGROUND:CREB-regulated transcription coactivator 3 (CRTC3) is found in adipocytes, where it may promote obesity through disruption of catecholamine signaling. We wished to assess whether CRTC3 is a soluble protein secreted by adipose tissue, explore whether CRTC3 is detectable and quantifiable in the circulation, and ascertain whether CRTC3 serum concentrations are related to metabolic markers in children. METHODS: Explants of adipose tissue from 12 children were cultured to study adipocyte cell size and the secretion of CRTC3 (immunoblot and ELISA). We also performed a cross-sectional and longitudinal study in 211 asymptomatic prepubertal white children at age 7 years, 115 of whom were followed up at age approximately 10 years. We measured circulating concentrations of CRTC3 and studied associations between serum CRTC3 and metabolic markers. RESULTS: Measurable concentrations of CRTC3 were found in conditioned media of adipose tissue explants and in serum samples. CRTC3 concentrations in visceral adipose tissue were negatively associated with adipocyte cell size and positively related to adipocyte cell number (P < 0.05). In the cross-sectional study, higher CRTC3 concentrations were associated with higher body mass index (P = 0.001), waist circumference (P = 0.003), and systolic blood pressure (P = 0.007) and lower high molecular weight adiponectin (P = 0.003). In the longitudinal study, serum concentrations of CRTC3 at age approximately 7 years were associated with changes in waist circumference (β = 0.254; P = 0.004; r = 0.145) and high molecular weight adiponectin (β=-0.271; P = 0.014; r = 0.101), respectively, at age approximately 10 years. CONCLUSIONS:CRTC3, a newly identified protein that is related to childhood obesity, is present in the circulation, partly as a result of adipose tissue secretion. Higher serum CRTC3 concentrations are related to and predict a poorer metabolic profile in children.
Authors: Kerstin Rohde; Maria Keller; Lars la Cour Poulsen; Torunn Rønningen; Michael Stumvoll; Anke Tönjes; Peter Kovacs; Annette Horstmann; Arno Villringer; Matthias Blüher; Yvonne Böttcher Journal: EBioMedicine Date: 2019-05-30 Impact factor: 8.143