The serum levels of the EGF-like homeotic protein dlk1 correlate with different metabolic parameters in two hormonally different children populations in Spain.
BACKGROUND
The Dlk1 gene encodes for dlk1, a transmembrane protein belonging to the EGF-like repeat-containing family. Dlk1 has been shown to act as a regulator of adipogenesis. Fc-dlk1 transgenic mice show a decrease in adipose tissue and glucose tolerance, hypertriglyceridaemia and lower insulin sensitivity. Dlk1-deficient mice show growth retardation, increased serum lipid metabolites and develop obesity. These data advocate for a role of dlk1 in the maintenance of lipid homeostasis, and suggest that dlk1 levels may influence the development of cardiovascular disease.


OBJECTIVE
In this study, we analysed whether dlk1 serum levels could be indicative of the different hormonal or metabolic status shown by two Spanish children populations (6-8 years-old), Orense and Murcia. We determined dlk1 serum levels by ELISA assay, using an antibody raised against the recombinant protein, and performed a correlation analysis against measurements of several hormonal and biochemical parameters in samples from 494 subjects.


RESULTS
We found a statistically significant positive correlation between serum levels of dlk1 and those of glucose (P < 0.05), total cholesterol (P < 0.01) and high-density lipoprotein-cholesterol (HDL-C) (P < 0.01) in children from Murcia, but not from Orense's population, where dehydroepiandrosterone-sulphate (DHEA-S) levels were significantly higher (P < 0.01) and dlk1 correlated positively with insulin (P < 0.01), homeostasis model assessment (HOMA) (P < 0.01) and free fatty acids (FFA) (P < 0.05).


CONCLUSIONS
dlk1 serum levels appear related to the anabolic status of the children in association with changes in the levels of DHEA-S, which have been associated with hyperinsulinaemia and diabetes. Monitoring dlk1 levels may be important to evaluate the metabolic and hormonal stage of child development.
Hermida
Carmen
C
Departamento de Bioquímica de la UAM, and Instituto de Investigaciones Biomédicas Alberto Sols UAM-CSIC, Facultad de Medicina de la Universidad Autónoma de Madrid, 28029. Madrid, Spain.
Garcés
Carmen
C
de Oya
Manuel
M
Cano
Beatriz
B
Martínez-Costa
Oscar H
OH
Rivero
Samuel
S
García-Ramírez
José J
JJ
Laborda
Jorge
J
Aragón
Juan J
JJ
D041721:3T3-L1 Cells; D000818:Animals; D041702:BALB 3T3 Cells; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002135:Calcium-Binding Proteins; D050260:Carbohydrate Metabolism / Q000502:physiology*; D002648:Child; D002657:Child Development / Q000502:physiology*; D006305:Health Status Indicators; D006728:Hormones / Q000032:analysis / Q000097:blood* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D050356:Lipid Metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000097:blood*; D051379:Mice; D010843:Pichia; D013030:Spain
D015415:Biomarkers; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins