1. Investigación

By using different experimental designs in the rat we have been able to answer several unanswered questions on the short- and long-term effects of alterations of lipid metabolism during the perinatal stage. The first was to demonstrate the importance of maternal body fat accumulation during the first half of pregnancy, since undernutrition in this critical period when fetal growth is slow, impedes fat depot accumulation and not only restrains intrauterine development but has long-term consequences, as shown by an impaired glucose tolerance when adults. Secondly, undernutrition during suckling has major long-term effect of decreasing body weight, even though food intake is kept normal from the weaning period. Our findings also show that a diet rich in n-3 fatty acids during pregnancy and lactation has adverse effects on offspring development, but cross fostered experiments showed that this effect was a consequence of the intake of these fatty acids during the lactation period rather than during pregnancy. Pups from dams that were fed a fish oil-rich diet during pregnancy and lactation were found to have altered glucose/insulin relationship at the age of 10 weeks. Since a n-3 fatty acid-rich diet decreases milk yield during lactation, additional experiments were carried out to determine whether decreased food intake or altered dietary fatty acid composition, or both, were responsible for the long-term effects on the glucose/insulin axis. Results show that the decreased food intake caused by a n-3 fatty acidrich diet rather than the change in milk composition during suckling was responsible for the reduced pancreatic glucose responsiveness to insulin release at 16 weeks of age. In conclusion, present findings indicate that impaired maternal fat accumulation during early pregnancy and food intake during lactation, rather than a difference in dietary fatty acid composition, have major effects on postnatal development and affect glucose/insulin relationships in adult rats.

During pregnancy, lipid metabolism plays a major role to warrant the availability of substrates to the foetus. By using different experimental designs in the rat we have been able to answer several questions that were open about the short- and long-term effects of alterations of lipid metabolism during the perinatal stage. The first one was to demonstrate the importance of maternal body fat depot accumulation during the first half of pregnancy. We found that conditions like undernutrition circumscribed to this specific period when foetal growth is still small, that impede such fat accumulation not only restrain intrauterine development but also have long-term consequences, as shown by an impaired glucose tolerance when adults. Secondly, undernutrition during suckling has major long-term effect decreasing body weight, even though food intake was kept normal from the weaning period. Present findings also show that a diet rich in co-3 fatty acids during pregnancy and lactation has negative effects on offspring development, but cross fostered experiments showed that the effect was a consequence of the intake of these fatty acids during the lactation period rather than during pregnancy. Pups from dams that were fed a fish oil-rich diet during pregnancy and lactation were found to have altered glucose/insulin relationship at the age of 10 weeks. Since a ro-3 fatty acid-rich diet decreases milk yield during lactation, additional experiments were carried out to determine whether decreased food intake, altered dietary fatty acid composition, or both were responsible for the long-term effects on the glucose/insulin axis. Results show that the decreased food intake caused by a ro-3 fatty acid-rich diet rather than the change in milk composition during suckling was responsible for the reduced pancreatic glucose responsiveness to insulin release at 16 weeks of age. In conclusion, present findings indicate that impaired maternal fat accumulation during early pregnancy and food intake during lactation, rather than a difference in dietary fatty acid composition have a greater influence on postnatal development and affect glucose/insulin relationships in adult rats.

During early pregnancy, long-chain polyunsaturated fatty acids (LC-PUFA) may accumulate in maternal fat depots and become available for placental transfer during late pregnancy, when the fetal growth rate is maximal and fetal requirements for LC-PUFAs are greatly enhanced. During this late part of gestation, enhanced lipolytic activity in adipose tissue contributes to the development of maternal hyperlipidaemia; there is an increase in plasma triacylglycerol concentrations, with smaller rises in phospholipid and cholesterol concentrations. Besides the increase in plasma very-low-density lipoprotein, there is a proportional enrichment of triacylglycerols in both low-density lipoproteins and high-density lipoproteins. These lipoproteins transport LC-PUFA in the maternal circulation. The presence of lipoprotein receptors in the placenta allows their placental uptake, where they are hydrolysed by lipoprotein lipase, phospholipase A2 and intracellular lipase. The fatty acids that are released can be metabolized and diffuse into the fetal plasma. Although present in smaller proportions, maternal plasma non-esterified fatty acids are also a source of LC-PU FA for the fetus, their placental transfer being facilitated by the presence of a membrane fatty acid-binding protein. There is very little placental transfer of glycerol, whereas the transfer of ketone bodies may become quantitatively important under conditions of maternal hyperketonaemia, such as during fasting, a high-fat diet or diabetes. The demands for cholesterol in the fetus are high, but whereas maternal cholesterol substantially contributes to fetal cholesterol during early pregnancy, fetal cholesterol biosynthesis rather than cholesterol transfer from maternal lipoproteins seems to be the main mechanism for satisfying fetal requirements during late pregnancy.