ESPE Abstracts (2015) 84 FC8.1

DLK1 Expression in Adipose Tissue Following Fetal Growth Restriction: Relation to Visceral Fat Expansion and Catch-Up Growth in Wistar Rats

Gemma Carreras-Badosaa,b, Xavier Remesarc, Anna Prats-Puiga,d, Ferran Diaz-Roldana,b, Estíbaliz Platero-Gutierreza,b, Jose-Maria Martinez-Calcerradaa,d, Francis de Zeghere, Lourdes Ibañezf, Judit Bassolsa,b & Abel Lopez-Bermejoa,b

aGirona Institute for Biomedical Research, Girona, Spain; bDr Josep Trueta Hospital, Girona, Spain; cUniversity of Barcelona, Barcelona, Spain; dEUSES University School, Girona, Spain; eUniversity of Leuven, Leuven, Belgium; fSant Joan de Déu Children’s Hospital, Barcelona, Spain

Background: DLK1 (PREF1) is a key inhibitor of adipogenesis and adipocyte differentiation. Adipose tissue expansion depends on adequate adipocyte differentiation. However, whether lower DLK1 expression facilitates adipose tissue expansion following fetal growth restriction is so far unknown.

Objective and hypotheses: To study the expression of DLK1 in the adipose tissue of prenatally growth-restricted rats and its relation to postnatal visceral fat and weight gain.

Method: Calorie restriction during gestation was used to induce intrauterine growth retardation in Wistar rats. Dams on a 50% calorie-restricted diet delivered growth-restricted pups with low birth weight (R). Restricted offspring fed a standard rat chow after birth showed catch-up growth (RC) whereas restricted offspring kept on a calorie-restricted diet did not show catch-up growth (RR). Weight gain, visceral fat (including retroperitoneal fat) and relative expression of DLK1 in retroperitoneal fat, as well as microscopic morphology of this fat pad, were postnatally assessed in the offspring (n=14 pups/group) at day 42 (prepubertal juvenile rats).

Results: RC pups showed higher postnatal weight gain, percentage of visceral fat, retroperitoneal fat and adipocyte size, and lower DLK1 expression in retroperitoneal fat compared with RR pups (all P<0.0001). In RC pups, DLK1 expression was negatively related to body weight (r=−0.863, P<0.0001), weight gain (r=−0.835, P<0.0001), visceral (r=−0.808, P<0.0001), and retroperitoneal fat (r=−0.800, P<0.001).

Conclusion: Our results show for first time that lower DLK1 expression in retroperitoneal fat relates to postnatal catch-up growth and visceral fat expansion in prenatally growth-restricted rats. Deregulated DLK1 expression in adipose tissue could be among the mechanisms involved in postnatal visceral fat accumulation following fetal growth restriction.

Funding: This study was supported by a grant from the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (ISCIII), Madrid, Spain (PI13/01257), project co-financed by Fondo Europeo de Desarrollo Regional (FEDER).