ESPE Abstracts (2019) 92 RFC4.3

Dysregulated Gene Expression Profile in Visceral Adipose Tissue of Juvenile Wistar Rats with Catch-Up Growth: Association with Fat Expansion and Metabolic Parameters

Esther Lizárraga-Mollinedo1, Gemma Carreras-Badosa1, Xavier Remesar2, Silvia Xargay-Torrent1, Berta Mas-Parés1, Anna Prats-Puig3, Francis de Zegher4, Lourdes Ibáñez5, Abel López-Bermejo1, Judit Bassols1


1Pediatrics, Girona Biomedical Research Institute (IDIBGI), Salt, Spain. 2Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, Barcelona, Spain. 3Department of Physical Therapy, EUSES University of Girona, Girona, Spain. 4Department of Development & Regeneration, University of Leuven, Leuven, Belgium. 5Endocrinology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain


Background: Accelerated catch-up growth following intrauterine growth restriction increases the risk of developing visceral adiposity and metabolic syndrome. Animal models of growth restriction during gestation have been developed as a powerful tool to provide insight into the underlying molecular mechanisms thereof.

Objective: To analyze the patterns of gene expression in the retroperitoneal adipose tissue of rats with intrauterine growth restriction and postnatal catch-up growth.

Methods: A Wistar rat model of catch-up growth following intrauterine growth restriction was used. Dams fed ad libitum delivered control pups (C) and dams on a 50% calorie-restricted diet during gestation delivered pups with low birth weight (R). Restricted offspring fed a standard rat chow showed catch-up growth (RC) but those kept on a calorie-restricted diet did not (RR). Microarray studies were performed in the retroperitoneal adipose tissue of postnatal day 42. Among the top twenty ranked genes with the highest fold change between RC and RR, yielded by microarray, we selected five genes to be validated by qRT-PCR.

Results: Of the total number of genes (n=23,188), we identified 570 as differentially expressed genes (Fold Change > 3-log2) in the retroperitoneal adipose tissue of RC vs RR (FDR-p value<0.05). Functional enrichment analysis revealed a global upregulation of genes involved in carbohydrate and lipid metabolism and a downregulation of genes linked to inflammation and immune response. Five genes representative of these main pathways (Npr3, regulation of blood pressure; Pnpla3, lipid metabolic processes; Slc2a4, brown fat cell differentiation; Serpina3n, inflammatory response; Serpina12, positive regulation of PI3K) were confirmed by qRT-PCR and showed associations with several metabolic parameters, including body weight, amount of brown adipose tissue, and serum insulin and lipids.

Conclusion: We have identified the differential expression pattern in visceral adipose tissue of juvenile Wistar rats with catch-up growth following intrauterine growth restriction. We suggest that the differential regulation of these genes may be involved in visceral fat expansion during catch-up growth in juvenile rats and in the predisposition of these animals to develop metabolic abnormalities.