Prenatal stress increases the obesogenic effects of a high-fat-sucrose diet in adult rats in a sex-specific manner

Abstract

Stress during pregnancy can induce metabolic disorders in adult offspring. To analyze the possible differential response to a high-fat-sucrose (HFS) diet in offspring affected by prenatal stress (PNS) or not, pregnant Wistar rats (n = 11) were exposed to a chronic mild stress during the third week of gestation. The aim of this study was to model a chronic depressive-like state that develops over time in response to exposure of rats to a series of mild and unpredictable stressors. Control dams (n = 11) remained undisturbed. Adult offspring were fed chow or HFS diet (20% protein, 35% carbohydrate, 45% fat) for 10 weeks. Changes in adiposity, biochemical profile, and retroperitoneal adipose tissue gene expression by real-time polymerase chain reaction were analyzed. An interaction was observed between HFS and PNS concerning visceral adiposity, with higher fat mass in HFS-fed stressed rats, statistically significant only in females. HFS modified lipid profile and increased insulin resistance biomarkers, while PNS reduced insulin concentrations and the homeostasis model assessment index. HFS diet increased gene (mRNA) expression for leptin and apelin and decreased cyclin-dependent kinase inhibitor 1A and fatty acid synthase (Fasn), whereas PNS increased Fasn and stearoyl-CoA desaturase1. An interaction between diet and PNS was observed for adiponutrin (Adpn) and peroxisome proliferator-activated receptor-γ coactivator1-α (Ppargc1a) gene expression: Adpn was increased by the PNS only in HFS-fed rats, whereas Ppargc1a was increased by the PNS only in chow-fed rats. From these results, it can be concluded that experience of maternal stress during intrauterine development can enhance predisposition to obesity induced by a HFS diet intake.

Keywords::

• Adiponutrin
• adipose tissue
• diet-induced obesity
• early life stress
• fecal corticosterone
• ingenuity

Acknowledgements

The authors are grateful to Veronica Ciaurriz for her technical laboratory support. The authors also appreciate the careful reading and correction of the last version by Alexandra Simpson for English quality.

Declaration of interest : The authors would like to thank Línea Especial (LE/97) from the University of Navarra and the Carlos III Health Institute (CIBER project, Spain; Grant No. CB06/03/1017) for the financial support of this study and “Asociación de Amigos de la Universidad de Navarra” and IBERCAJA (Spain) for the doctoral fellowships of Ana Laura De la Garza and Laura Paternain. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.