Prenatal stress mediates tissue specific programming of 11β-hydroxysteroid dehydrogenase type 1 expression in diet-induced obese and dietary resistant rats

Abstract Background The link between uterine stress and fetal programming of metabolic diseases in the offspring is well established. However, susceptibility to prenatal stress-induced programming of metabolic diseases is not uniform across population. We have previously reported that diet-induced obese rats (DIO) are more susceptible to develop metabolic diseases in response to prenatal stress and postnatal HF diet challenge when compared to dietary resistant rats (DR), but the mechanism behind this phenomenon is unclear. In the present study, we hypothesized that prenatally stressed DIO rats will have alterations in stress axis and 11βHSD1 expression, which in turn predisposes them to metabolic disorders.Methods Pregnant DIO and DR rats were divided into 2 groups: control (normal pregnancy) and prenatal stress (restraint stress during the last week of gestation) groups. The male offspring were weaned onto chow diet until 9 weeks of age and then shifted to either chow or HF diet (45% calories from fat) for 1 week. Following 1 week of chow/HF diet treatment, the animals were sacrificed, and tissues were collected for assessing stress axis activity and 11βHSD1 expression.Results Prenatal stress activated stress axis with increased NE levels in the PVN and CRH levels in the median eminence in both DIO and DR rats. Though there was no change in either circulating CORT levels or adrenal gland weight, 11βHSD1 protein expression increased significantly in adipose tissue of prenatally stressed DIO and DR offspring compared to controls. Baseline levels of 11βHSD1 protein in the adipose tissue were higher in DIO than DR animals implicating a role for 11βHSD1 in the development of obesity. Postnatal HF diet did not have any additive effect on prenatal stress-induced changes.Conclusion Our results suggest that stress axis activation with induction of adipose tissue 11βHSD1 might be involved in the fetal origins of metabolic diseases.