Intrauterine growth restriction combined with a maternal high-fat diet increased adiposity and serum corticosterone levels in adult rat offspring.

Abstract

Intrauterine growth restriction (IUGR) and fetal exposure to a maternal high-fat diet (HFD) independently increase the risk of developing obesity in adulthood. Excess glucocorticoids increase obesity. We hypothesized that surgically induced IUGR combined with an HFD would increase adiposity and glucocorticoids more than in non-IUGR offspring combined with the same HFD, findings that would persist despite weaning to a regular diet. Non-IUGR (N) and IUGR (I) rat offspring from dams fed either regular rat chow (R) or an HFD (H) were weaned to either a regular rat chow or an HFD. For non-IUGR and IUGR rats, this study design resulted in three diet groups: offspring from dams fed a regular diet and weaned to a regular diet (NRR and IRR), offspring rats from dams fed an HFD and weaned to a regular diet (NHR and IHR) and offspring from dams fed an HFD and weaned to an HFD (NHH and IHH). Magnetic resonance imaging or fasting visceral and subcutaneous adipose tissue collection occurred at postnatal day 60. IHH male rats had greater adiposity than NHH males, findings that were only partly normalized by weaning to a regular chow. IHH male rats had a 10-fold increase in serum corticosterone levels. IHH female rats had increased adiposity and serum triglycerides. We conclude that IUGR combined with an HFD throughout life increased adiposity, glucocorticoids and triglycerides in a sex-specific manner. Our data suggest that one mechanism through which the perinatal environment programs increased adiposity in IHH male rats may be via increased systemic glucocorticoids.