Effect of maternal diet on fetal hepatic lipogenesis

Abstract

The effects of: a, maternal diet; b, cyclic-3',5'- adenosinemonophosphate (cyclic AMP) and c, clofibrate on hepatic lipogenesis in fetal rats were studied. The experimental diets contained 22% protein, 40–50% carbohydrate, adequate vitamins, and minerals. In addition, the fat-containing diets were supplemented with either 15% corn oil, 25% corn oil, or 5% cholesterol + 10% oleic acid. In the clofibrate feeding studies 0.3% (w/v) of the ethyl ester was added to a stock ration or to fat-free diet. Lipogenesis was measured in liver slices incubated with [2- 14C]pyruvate, [1- 14C] acetate, or 3H 2O. In addition, activities of lipogenic enzymes were measured in cytosol fractions from liver homogenates. The effects of the experimental diets on liver composition were also examined. Lipogenic activity was higher in fetal than in maternal liver. When 15% corn oil was added to the maternal diet, fatty acid synthesis in fetal liver did not decrease as it did in maternal liver. Maternal fasting decreased fetal fatty acid synthesis by 50% when measured with 14 C and less than 10% when measured with 3H 2O. Although the addition of cholesterol to the maternal diet decreased cholesterol synthesis in maternal liver, no such decrease was observed in fetal liver. Changes in enzyme activities paralleled alterations in lipogenesis in maternal but not in fetal liver. Corn oil feeding or fasting increased the rate of transfer of linoleate from the dam to the fetus. However, accumulation of linoleate in fetal liver did not correlate with a decreased rate of fatty acid synthesis as it did in maternal liver. Maternal hepatic glycogen stores were depleted by fasting, but glycogen levels in fetal liver remained high under these conditions. Chemical degradation of the fatty acids synthesized by slices (radioactivity in total molecule/radioactivity in carboxyl carbon) was used to determine the relative contributions of the de novo and chain elongation pathways to total fatty acid synthesis. The high percentage of de novo fatty acid synthesis in fetal liver was not affected by maternal dietary treatments. Experiments with cyclic AMP and clofibrate tested two possibilities: a, whether known inhibitors of lipogenesis will inhibit fetal hepatic lipogenesis; b, whether inhibitors present in the maternal circulation can reach their site of action in the fetus. Since lipogenesis in slices of fetal liver was inhibited by in vivo or in vitro addition of clofibrate and in vitro addition of cyclic AMP, there are no fundamental differences in fetal hepatic lipogenesis that prevent response to known inhibitors. These results imply that if an inhibitor from the maternal circulation can reach its site of action in the fetus, it will inhibit lipogenesis. Inhibitors of lipogenesis produced in the mother in response to dietary treatment do not reach the fetal liver.