Paradoxical Increase in Maternal Plasma Leptin Levels in Food-Restricted Gestation: Contribution by Placental and Adipose Tissue

Abstract

Maternal food restriction (FR) during pregnancy results in decreased body weight with increased plasma leptin. To address this paradox, we investigated the effects of FR during pregnancy on growth and leptin levels in maternal, placental, and fetal sites. From embryonic day E10, control pregnant rats received ad libitum (AdLib) food, whereas study rats were 50% FR. At gestational ages, E16 and E20, the alterations in maternal body composition, retroperitoneal versus subcutaneous adipose leptin expression, and plasma leptin levels were studied. Furthermore, these changes were related to non-pregnant (NP) status and placental/fetal growth and leptin levels. As compared to NP, both FR and AdLib dams showed a progressive increase in body and lean body mass. However, total body fat was reduced in FR dams but remained unchanged in AdLib dams. Furthermore, plasma leptin levels in FR dams were markedly increased at E20 unlike AdLib dams, which showed moderate increments at E16 and E20. Additionally, FR dams showed significantly decreased leptin expression in subcutaneous and notably unaltered levels in retroperitoneal adipose tissue, suggesting an alternate source of elevated maternal plasma leptin. More importantly, the FR dams had reduced placental weights with paradoxical increased leptin expression at both gestations. Thus, increased plasma leptin levels at E20 in maternal FR pregnancies may be explained, in part, by upregulation of placental leptin. Despite maternal and placental hyperleptinemia during FR pregnancies, the growth-restricted FR fetus had reduced leptin levels. These findings have important implications for pregnancy outcome and fetal growth.