The long-term goal of this laboratory is to determine the critical processes in lipid metabolism that are essential for perinatal growth and development. Optimal fetal growth is critically linked to placental growth and function, but a manor area of placental growth has been understudied: glycerolipid metabolism. In the placenta, glycerolipids are essential for cellular membranes, intracellular signals such as prostaglandins and diacylglycerol, and triacylglycerol energy stores. In addition, as much as 50% of the daily fatty acid requirement of the fetus is transported by the placenta. For the fetus, fatty acids are additionally required for the synthesis of secreted products that are essential for postnatal life such as bile, serum lipoproteins and pulmonary surfactant. Little is known about placental lipid metabolism on the molecular level. Thus the proposed studies are designed to provide basic information on enzyme pathways that facilitate fatty acid incorporation into complex lipids within the placenta and fatty acid release from placenta cells. We will identify and characterize critical enzymes of complex lipid metabolism in placenta, and identify the regulatory controls on lipid synthesis and fatty acid release. Cultured trophoblast cells will be used to study placental glycerolipid metabolism. Preliminary data are consistent with the hypotheses that 1) trophoblast cells synthesize fatty acids de novo and release them and that 2) trophoblast release of fatty acid requires intermediate esterification steps to form both triacylglycerol and one or more phopholipid species. Studies will be performed using isolated human and guinea pig trophoblast cells that have been incubated with radiolabeled lipid precursors in order to identify the species of complex lipids that release fatty acids. Use of trophoblast cells in a perifusion system will allow us to examine acute hormone and substrate regulation of lipid metabolism. We will identify cellular glycerolipid precursors. Specific points of regulation will point out the synthetic and hydrolytic enzyme activities that play critical roles in this process. These activities will be characterized in human and guinea pig placenta during gestation.
| Igal, R A; Rhoads, J M; Coleman, R A (1997) Neutral lipid storage disease with fatty liver and cholestasis. J Pediatr Gastroenterol Nutr 25:541-7 |
| Garner, S C; Chou, S C; Mar, M H et al. (1993) Characterization of choline metabolism and secretion by human placental trophoblasts in culture. Biochim Biophys Acta 1168:358-64 |
| Williams, M L; Coleman, R A; Placezk, D et al. (1991) Neutral lipid storage disease: a possible functional defect in phospholipid- linked triacylglycerol metabolism. Biochim Biophys Acta 1096:162-9 |
