Preferential uptake of long chain polyunsaturated fatty acids by isolated human placental membranes

Abstract

Fatty acid uptake by the placenta is thought to be a carrier-mediated process, however the mechanism by which long chain polyunsaturated fatty acids (LCPUFA) are preferentially accumulated from the maternal circulation to the fetal tissues is still unclear. To examine the role of the placenta in this process, binding of four different radiolabelled fatty acids (-14C-oleate, -14C-linoleate, [14C]a-linolenate and [14C]arachidonate) to human placental membranes was studied. Binding of fatty acid was found to be time- and temperature dependent. At equilibrium, the total binding of oleate was highest (5.1 +/- 0.1 nmoles/mg protein) followed by linoleate (2.8 +/- 0.31 nmoles/mg protein) and arachidonate (2.06 +/- 0.4 nmoles/mg protein) and alpha-linolenate binding was lowest (0.5 +/- 0.1 nmoles/mg protein). However, oleate had the lowest specific binding (37% of the total binding) whereas arachidonate had the highest specific binding (approximately 86% of the total binding) followed by linoleate and a-linolenate (62%, and 69% of the total binding, respectively). Binding of each [14C] fatty acid was also assessed in the presence of 20-fold excess of other unlabelled ligands. Binding sites seem to have preference for the binding of [14C] fatty acids in the following order: arachidonic acid >>> linoleic acid >> a-linolenic acid >>>>> oleic acid, whereas BSP and a-tocopherol did not show any competition with any of the [14C] fatty acids. These data suggest that the fatty acid binding sites in placental membranes are specific for the fatty acids but that they have heterogeneous affinities. Trans fatty acids (elaidic and linoelaidic acids) also competed very strongly for the [14C] fatty acid binding. Polyclonal antiserum raised against placental FABPpm inhibited binding of these [14C] fatty acids but with variable degrees of inhibition; EFA/LCPUFA binding was much more than that of oleate. Our data suggest that EFA/LCPUFA bound to albumin are preferentially transported by human placental membranes and that the placental FABPpm may be involved in the sequestration of EFA/LCPUFA by the placenta.

Relationship between plasma fatty acid profile and antioxidant vitamins during normal pregnancy

“…The enhanced proportion of these fatty acids in cord blood plasma in contrast to the limited placental transfer for saturated fatty acids as compared to PUFA (Campbell et al, 1996;Haggarty et al, 1997) would indicate an active lipogenesis in the fetus, as demonstrated in previous studies (Dunlop & Court, 1978). Similar reasoning could be used to justify the high proportion of oleic acid in cord blood plasma, although slightly lower than in the mothers during late gestation.…”

“…Similar reasoning could be used to justify the high proportion of oleic acid in cord blood plasma, although slightly lower than in the mothers during late gestation. Placental transfer of oleic acid is also lower than that of PUFA (Campbell et al, 1996;Haggarty et al, 1997), and therefore its proportional abundance in the fetus may reflect an active desaturation of stearic acid.…”

Adaptation of maternal lipid flux to pregnancy: Research needs

“…Arachidonate is also an important precursor for lipid signaling molecules. Since LC-PUFA are synthesized in insuf®cient quantity by the fetus, and the placenta apparently does not possess the D5 and D6 desaturase activities to convert essential fatty acids to LC-PUFA (reviewed in Crawford, 1993;Campbell et al, 1996), mechanisms for the preferential synthesis and transfer of these fatty acids to the fetus and placenta must be in place. Since these mechanisms are at the core of the most important questions concerning lipid metabolism in pregnancy, the focus of this discussion will be the problem of providing LC-PUFA to the fetus.…”

“…The ®rst is the presence of a plasma membrane fatty acid binding protein (FABP PM in Figure 1). FABP PM was identi®ed in human and sheep placenta by Campbell et al (1996) and the order of preference for the four fatty acids studied was arachidonic ) linoleic ) a-linolenic b b b b b oleic acid. Trans fatty acids inhibited the binding ef®ciently.…”

“…As far as is known, triglycerides are not transported across the placenta intact (Campbell et al, 1996), although it is possible that this statement needs to be reevaluated in light of the high concentration of VLDLR in the placenta. Instead, lipoprotein lipase hydrolyzes the triglycerides to their component fatty acids making them available for transfer to the fetus.…”