Intrauterine growth restriction induced alterations in the endocannabinoid system of rats

Intrauterine growth restriction (IUGR) is most commonly caused by uteroplacental insufficiency (UPI). Individuals born IUGR are at an elevated risk for developing adult obesity and other metabolic complications. The endocannabinoid (EC) system is involved in the stimulation of adipose lipogenesis and glucose homeostasis. Over stimulation of the peripheral EC system can lead to the development of obesity and type 2 diabetes. The actions of the EC ligands are mediated by EC receptors, CB1 and CB2, while ligand degradation is arbitrated via the action of Fatty acid amide hydrolase (FAAH). Despite the connection between obesity and the EC system, the impact of IUGR on adipose CB receptor expression levels is unknown. IUGR rat adipose tissue was compared to control animal tissue. CB1, CB2 and FAAH mRNA transcript levels were measured using real time PCR at day 21 of life in male and female subcutaneous and retroperitoneal adipose tissue. Additionally, western blotting was used to compare protein levels of these receptors in both fat depots. Results are expressed as a % of control +/- standard error of the mean (SEM). IUGR significantly increased CB2 receptor mRNA levels in subcutaneous adipose tissue of male (535.1% +/- 105.9 [p<0.05]) and female (947.7% +/- 214.8 [p<0.05]) rats at d21. CB1 receptor levels were decreased in the subcutaneous adipose tissue in IUGR males (55.2% +/- 5.2 [p<0.05]) but were unchanged in females. FAAH mRNA levels were increased in both subcutaneous and retroperitoneal adipose depots in male rats (323.7% +/- 41.1 [p<0.05], 237.9% +/- 43.9 [p<0.05], respectively), with no change in female animals. A decrease in FAAH mRNA levels was observed in retroperitoneal adipose tissue of female rats (51.0% +/- 9.3 [p<0.05]). Protein levels of CB2 receptor in the subcutaneous adipose of both males and females were significantly increased (463.9 +/- 76.5 [p<0.05], 185.1 +/-16.2 [p<0.05], respectively). In conclusion, IUGR increases CB2 receptor mRNA and protein levels in the subcutaneous adipose tissue of both male and female rats at d21 as well as FAAH mRNA levels in both adipose depots in male rats, before the onset of obesity. This data may help explain the link between the increased risk of metabolic consequences experienced later in life as a result of the IUGR condition and the EC system.