ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2025
Dysregulated Fatty Acid Metabolism in Preeclampsia Among Highland Andeans: Insights Into Adaptive and Maladaptive Placental Metabolic Phenotypes.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- Reduced serum acetyl-L-carnitine is associated with hypertensive disorders in women with gestational diabetes mellitus: a multi-omics study.Cardiovascular diabetology · 2026Article
- Dysregulated Fatty Acid Metabolism in Preeclampsia Among Highland Andeans: Insights Into Adaptive and Maladaptive Placental Metabolic Phenotypes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
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15 authors.
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Abstract
High-altitude pregnancy presents the complex physiological challenge of fulfilling maternal, placental, and fetal metabolic demands under chronic ambient hypoxia. Highland Andeans exhibit signs of adaptation to high-altitude hypoxia, showing relative protection against altitude-associated fetal growth restriction (FGR) and the positive selection of metabolic genes linked to placental mitochondrial capacity. Not all infants are protected, with both FGR and preeclampsia occurring among highland-resident Andeans. In Andeans, placental metabolic dysfunction is evident. By integrating metabolomic studies of maternal-placental-fetal triads with adaptive genetic signals in the fetal genome, we sought to identify adaptive and maladaptive placental metabolic phenotypes in highland Andeans (La Paz, Bolivia; 3850 m), including normotensive and preeclamptic pregnancies. Widespread differences in metabolite abundance were evident between normotensive and preeclamptic pregnancy across maternal, placental, and fetal compartments. Preeclampsia was characterized by a pronounced accumulation of fatty acid derivatives, specifically medium and long-chain acylcarnitines; these were also associated with low birth weight. Genotype-phenotype association analyses revealed novel links between putatively adaptive fetal haplotypes and placental metabolite abundance. Carriers of specific adaptive fetal haplotypes comprising genes linked to lipid metabolism had a greater abundance of placental short-chain acetyl-carnitine alongside decreased levels of linolenic acid (CPT2/LRP8), lower levels of the medium-chain octanoylcarnitine (EXOC4), and greater abundance of free carnitine (LIPG). Collectively, our study reveals a distinct metabolic phenotype in Andean preeclampsia characterized by incomplete fatty acid oxidation and highlights novel links between putatively adaptive fetal haplotypes and healthy placental metabolic phenotypes.
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