title: Gestational diabetes mellitus decreases placental uptake of long-chain polyunsaturated fatty acids: involvement of long-chain acyl-CoA synthetase.
abstract: The long-chain polyunsaturated fatty acids (LC-PUFAs) arachidonic (AA) and docosahexaenoic (DHA) acids are essential for fetal development. Gestational diabetes mellitus (GDM) is a pregnancy disorder associated with perinatal and lifelong risk complications for both the mother and the newborn. Our aim was to investigate the influence of GDM, and some of its associated conditions, upon the placental uptake of AA and DHA. Uptake of (14)C-AA and (14)C-DHA by human trophoblasts obtained from normal pregnancies (NTB cells) was mediated by both saturable (for lower substrate concentrations) and non-saturable (for higher substrate concentrations) mechanisms. Uptake of both fatty acids was inhibited by other LC-PUFAs and, markedly, by the long-chain acyl-CoA synthetase (ACSL) inhibitor, triacsin C. Human trophoblasts obtained from GDM pregnancies (DTB cells) showed a significantly lower (14)C-AA and (14)C-DHA accumulation, through a decrease in both the saturable and the non-saturable components of uptake, which was associated with a decrease in ACSL1 mRNA levels. Uptake of LC-PUFAs by NTB cells increased (by 20-25%) after short-term exposure to TNF-α ((14)C-AA and (14)C-DHA) and insulin ((14)C-DHA). In conclusion, GDM, distinctly from its associated conditions, markedly decreases placental uptake of LC-PUFAs, which probably contributes to the deleterious effects of this disease for the newborn.
authors.affiliation: Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: João R
authors.initials: JR
authors.lastname: Araújo
authors.forename: Ana
authors.initials: A
authors.lastname: Correia-Branco
authors.forename: Carla
authors.initials: C
authors.lastname: Ramalho
authors.forename: Elisa
authors.initials: E
authors.lastname: Keating
authors.forename: Fátima
authors.initials: F
authors.lastname: Martel
mesh_terms: D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors / Q000502:physiology*; D016640:Diabetes, Gestational / Q000503:physiopathology*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014226:Triazenes / Q000494:pharmacology; D014327:Trophoblasts / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D014226:Triazenes; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; C034613:triacsin C; D003066:Coenzyme A Ligases; C583414:ACSL1 protein, human
keywords: Gestational diabetes; Long-chain polyunsaturated fatty acids; Placentae; Transport