234: Leptin Mediated Model of Pre-Eclampsia in Mice

Leptin while known to regulate energy and glucose metabolism, has also been shown to increase blood pressure (BP) through receptors in the hypothalamus. Pregnancy is a state of hyperleptinemia and of leptin resistance through decreased expression of receptors in the hypothalamus and decreased transport to the brain. Abnormally increased circulating leptin levels have been observed during pre-eclampsia. Given these associations, we hypothesize that leptin may have a role in the pathogenesis of pre-eclampsia. Wild-type mice were separated into non-pregnant (NP, n=4), pregnant with saline pumps (P+S, n=4), and pregnant with leptin pumps (P+L, n=6) infusing 2.4 mcg/g/d with all mice being assessed for BP, body weight (BW), serum leptin, and urine protein. After delivery, each placenta was weighed and the pups measured for BW and length. A separate group of wild-type mice had intracerebroventricular (ICV) cannulation, and then were separated into ICV with saline (ICV P+S) versus ICV with leptin (ICV P+L) of 2mcg/day and were assessed for BP and BW. P+L had elevated leptin levels in the blood compared to NP (p < 0.001) and P+S (p < 0.001). P+S had elevated leptin levels compared to NP (p < 0.05). When compared to P+S, P+L had smaller placentas (p < 0.01), pups with lower BW (p < 0.05), and shorter length (p < 0.05). Urine protein levels were not statistically different between P+S and P+L. BP was not statistically different between the 3 experimental groups. However, when ICV leptin was given (ICV P+L), a significant increase in BP was observed compared to ICV P+S (p < 0.01). ICV leptin administration did not affect body weight gain compared to saline ICV administration (ICV P+S). Peripheral administration of leptin had a significant effect on placental weight and pup growth. However, only centrally administered leptin altered BP. Given known changes in leptin receptors and transport into the brain during pregnancy, our results suggest that the abnormal increase in leptin levels during pre-eclampsia may be involved in the pathogenesis of the disorder. While peripheral leptin may interfere with the placental and embryo growth, derangements in leptin transport into the brain in pre-eclamptic patients may affect blood pressure.