Essential fatty acids in the perinatal period. Short and long term effects in a rat model

Abstract: Nutritional factors during a sensitive perinatal period may lead to developmental adaptations proposed to program for pathological conditions later in life. An adequate supply of essential fatty acids (EFA) during pregnancy and lactation is crucial for optimal fetal and postnatal development. In animals and man, variations in the levels of EFA and in the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) affect growth, development of the neuroendocrine and the immune systems of the offspring and might also have additional effects later in life via, for instance, leptin-associated mechanisms. The major aim of the study was to investigate whether variation in the type of dietary EFA during pregnancy and lactation in rats could modulate neonatal leptin levels and induce developmental adaptations that may persist into adulthood.A deficiency of both n-6 and n-3 EFA in the maternal diet resulted in decreased serum leptin levels in the offspring associated with reduction of both the amount of inguinal white adipose tissue (WAT) and the leptin mRNA expression in inguinal WAT. In addition, deficiency of EFA in the maternal diet affected also the milk leptin levels, which were higher in the EFA deficient dams than in the controls at 3 weeks of lactation. The serum leptin levels during the first week of age was two-fold less in the pups of dams fed the diet enriched in n-3 PUFA (n-3 diet) compared to the those fed the diet containing nine-fold more n-6 PUFA than n-3 PUFA (n-6/n-3 diet). Further increase in the dietary intake of n-6 PUFA (n-6 diet) did not elevate the leptin levels in the pups compared to the n-6/n-3 group. Both the lower adipose tissue mass and smaller adipocyte size could explain the lower serum leptin levels in the n-3 group. The data demonstrate that the total intake and the ratio of the n-3 and n-6 PUFA in the mother's diet modulated neonatal leptin levels. Furthermore, the maternal n-6/n-3 diet promoted increase in body weight, inguinal WAT mass and adipocyte size and suppressed leptin mRNA levels in WAT in the offspring. In order to study the long-term effects of the dietary intake of n-6 in relation to n-3 PUFA during the perinatal period, all offsprings were weaned onto an ordinary chow and followed up until 30 weeks of age. At postnatal week 28 the food intake and the mean body weight were significantly higher in the offsprings of the dams fed the n-6/n-3 diet during pregnancy and lactation compared to the other two diet groups. The fasting plasma insulin concentration was elevated in both the adult male and female rats of the n-6/n-3 group, but the systolic blood pressure was only increased in the adult male rats. The data suggest that the ratio of the n-6 to n-3 PUFA in the mother's diet have important long-term effects in the offspring. Variations in the dietary intake of PUFA during pregnancy and lactation seem to be important for development and programming, influencing the health of the offspring in adult life.