Leptin, fetal nutrition, and long-term outcomes for adult hypertension

One factor contributing to later hypertension, particularly in response to nutritional challenges is excess fat deposition around the kidney. In this review we discuss the hypothesis that these adverse conditions can be entrained by exposure of the conceptus to maternal nutrient restriction in early pregnancy. To this end we have shown in sheep that maternal nutrient restriction coincident with the time of embryogenesis and placental growth results in an early increase in fetal fat mass around the kidney that persists into later life. This is accompanied by an increase in leptin mRNA abundance and growth factor sensitivity. These adaptations occur in conjunction with reduced maternal plasma cortisol, thyroid hormones and leptin concentrations over the period of nutrient restriction. Some, but not all of these effects on fat development are accompanied by long term cardiovascular adaptations. As young adults, offspring from mothers nutrient restricted between early to mid gestation exhibit a leftward resetting, and blunting, of the cardiovascular baroreflex that appears to be mediated centrally through altered regional angiotensinogen II activity. At the same time, fat mass remains raised in nutrient restricted offspring. These animals demonstrate a marked increase in plasma leptin following sympathetic stimulation which is not observed in controls that indicates resetting of adipocyte sensitivity to stress. In conclusion, global nutrient restriction confined to the periods of embryonic and placental development therefore, programmes adult physiology, which may enhance predisposition to later disease given the appropriate environmental stimuli.