SAT-LB041 Insulin and IGF-2 Equally Regulate Placental Triglyceride Content

Background: Obesity affects 25% of pregnant women and is associated with a higher risk of neonatal complications, such as macrosomia and increased adiposity. In addition to transporting maternal nutrients to the fetus, the placenta receives maternal hormone signals and synthesizes paracrine hormones which influence nutrient flux to the fetus. Obese women were shown to have higher placental lipid content compared to lean women, but the regulation of placental lipid metabolism is unknown. We hypothesized that insulin regulates lipid metabolism in the placenta by activating IR-B, which is the insulin receptor (IR) isoform characterized as having metabolic activity. Methods: Healthy, lean women (n=7) of mean age 34.4 ± 1.4 years and BMI 21.5 ± 0.5 kg/m(2) consented for placental collection at elective c-section. Full thickness placental samples from multiple quadrants were obtained. Villous explants were cultured for 24 hours. After 4-hour starvation, explants were treated for 48 hours with insulin 100nM, IGF-1 100nM, IGF-2 100nM, or vehicle. Lipids were extracted from homogenized explants using a chloroform-methanol separation protocol. Triglyceride (TG) content was quantified by colorimetric spectrophotometer and normalized to explant weight. Data were analyzed by one-way ANOVA with a Tukey’s multiple comparisons test. Results: In placenta explants from lean women, insulin induced a 2.5-fold increase in triglyceride content, relative to vehicle (19.8 ± 3 vs 7.3 ± 1.5 mcg/mg, p= 0.002). Similarly, IGF-2 promoted a 3.4-fold increase compared to vehicle-treated placental tissue (24.9 ± 3.3 mcg/mg, p= 0.0002). In contrast, IGF-1 did not significantly alter TG levels (12.7 ± 2.9 vs 10.2 ± 2.6 mcg/mg, p= NS). Conclusions: We show that placental triglyceride content is equally regulated by maternal insulin and placenta-synthesized IGF-2. Since IGF-2 has a high affinity for IR-A and minimal affinity for IR-B, these data indicate that IR-A likely plays a key role in placental lipid metabolism. These findings are novel since IR-A activity is generally characterized as mitogenic, rather than metabolic. Notably, IGF-1, which activates IGF-1R, does not play a role in placental lipid metabolism in vitro. Hyperinsulinemia due to maternal obesity may alter placental triglyceride storage and thus promote neonatal adiposity through greater availability, independent of circulating maternal triglyceride levels. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.