Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseases.
The role of fat metabolism during human pregnancy and in placental growth and function is poorly understood. Mitochondrial fatty acid oxidation disorders in an affected fetus are associated with maternal diseases of pregnancy, including preeclampsia, acute fatty liver of pregnancy, and the hemolysis, elevated liver enzymes, and low platelets syndrome called HELLP. We have investigated the developmental expression and activity of six fatty acid beta-oxidation enzymes at various gestational-age human placentas. Placental specimens exhibited abundant expression of all six enzymes, as assessed by immunohistochemical and immunoblot analyses, with greater staining in syncytiotrophoblasts compared with other placental cell types. beta-Oxidation enzyme activities in placental tissues were higher early in gestation and lower near term. Trophoblast cells in culture oxidized tritium-labeled palmitate and myristate in substantial amounts, indicating that the human placenta utilizes fatty acids as a significant metabolic fuel. Thus human placenta derives energy from fatty acid oxidation, providing a potential explanation for the association of fetal fatty acid oxidation disorders with maternal liver diseases in pregnancy.
Shekhawat
Prem
P
Departments of Pediatric,Washington University School of Medicine, St Louis, Missouri 63110, USA. pshekhawat@mail.mcg.edu
Bennett
Michael J
MJ
Sadovsky
Yoel
Y
Nelson
D Michael
DM
Rakheja
Dinesh
D
Strauss
Arnold W
AW
D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000201:enzymology / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008107:Liver Diseases / Q000201:enzymology / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010920:Placenta / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000201:enzymology / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism
D005227:Fatty Acids