Fatty Acid Uptake in Placenta Promotes Adverse Fetal Outcomes in Cardiovascular Kidney Metabolic Syndrome Disorders of Pregnancy

Obesity is a key driver of Cardiovascular, Kidney, Metabolic Syndrome (CKMS). CKMS presents as cardiovascular disease, notably hypertension, renal and metabolic abnormalities including insulin resistance. Obese women are at high risk for CKMS-related pregnancy disorders, notably preeclampsia and gestational diabetes. Emerging clinical literature suggests circulating and placental lipid imbalance is a frequent finding of preeclampsia and gestational diabetes patients. We sought to utilize both human tissues and a novel preclinical model of CKMS of pregnancy to test the hypothesis that placentas from both mice and humans with CKMS demonstrate dysregulated fatty acid deposition that correlate with adverse fetal outcomes. To perform our preclinical study, we utilized our newly characterized CKMS model, the Agouti obese mouse, in pregnancy. We bred Agouti obese (n=8) and C57BL6 lean (n=9) with age-matched male mice 12-14 wks of age. We performed Doppler ultrasound (uterine artery resistance index (UARI) and echocardiogram) at gestation day (GD 15), glucose tolerance (GD15) and wire myography for vascular function (GD18). On GD18 mice were sacrificed and pups weighed. We collected placentas from lean and obese CKMS patients at WellstarMCG Health (Augusta, Ga, USA). In both mice and human placentas, we conducted liquid chromatography mass spectrometry to measure fatty acids. We analyzed by Student’s t-test or 2-W ANOVA w/RM, *=P< 0.05. Agouti weighed more than lean in nonpregnancy (46.5g±1.2 agouti vs 22.9g±0.4 lean*) and at GD18 (44.6g±1.0 agouti vs 26.9g±0.4 lean*) and had pronounced glucose intolerance, by 120 min fasting test (time-response curve, 2-W ANOVA w/RM*) both prior to pregnancy and at GD18. Nonpregnant and GD18 agouti exhibited endothelial dysfunction in 2nd order mesenteric arteries (concentration response curve of Acetylcholine (ACh) dilation, 2-W ANOVA w/RM*). Nitric oxide (NO) inhibition (LNAME) blunted differences in ACh-mediated relaxation, suggesting impaired NO in vasculature of Agouti mice. Agouti mice had lower fetal weights (626mg±22 agouti vs. 804mg±33 lean*) and placental efficiency (6.3±0.3 agouti vs 8.6±0.3* lean). There was no significant difference in UARI and ejection fraction at GD15, but relative left ventricular wall thickness trended to increase in Agouti compared to lean (0.68 ± 0.1 agouti vs 0.48±0.1 lean*). At GD18, Agouti mice have a lower heart/body weight ratio than lean mice (3.6g ± 0.2 agouti vs 4.6g ± 0.3 lean*). Placentas from Agouti mice demonstrated elevated relative lipid abundance than lean, with similar percentage of saturation and triacylglycerol content. Placentas from obese CKMS patients (n=6/group) demonstrated suppression of both free fatty acids and triacylglycerols compared to lean patients. These data indicate striking differences between mice and human placenta lipid deposition in obese CKMS pregnancy and prompt investigation into mechanisms whereby fatty acids in placenta may crosstalk with adverse maternal and fetal cardiovascular and metabolic outcomes. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.