Fatty acid oxidation in the human fetus: implications for fetal and adult disease.
Studies in the last few years have shown a remarkably high activity of fatty acid oxidation (FAO) enzymes in human placenta. We have recently shown mRNA expression as well as enzymatic activity of long-chain FAO enzymes in the human embryo and fetus. In this study we show activity of the FAO enzymes carnitine palmitoyltranferase 1, medium-chain acyl-CoA dehydrogenase and short-chain hydroxyacyl-CoA dehydrogenase in embryonic and fetal tissues. In addition, we show the presence of different acylcarnitines in fetal liver and kidney, which substantiates the notion that the mitochondrial FAO enzymes are not only present in human fetal tissues but also metabolically active. In a glucose-rich environment FAO might be necessary for additional ATP production from fatty acids, but also for the breakdown of fatty acids that are products of the turnover of membranes in the growing fetus. The importance of FAO in the human embryo and fetus is further stressed by the fact that a higher frequency of prematurity, intrauterine growth retardation, fetal morbidity and intrauterine death is noted in long-chain FAO defects. Furthermore, in animal studies, gestational loss during early embryonic development has been observed as a consequence of disturbed FAO. Finally, there are indications that regulation of activity of FAO during fetal development might not only be important for fetal life but may also have implications for health and disease in adulthood.
Oey
Nadia A
NA
Department of Pediatrics, G8-205, Emma Children's Hospital AMC, Academic Medical Centre, PO Box 22660, NL-1100 DD, Amsterdam, The Netherlands.
Ruiter
Jos P N
JP
Attié-Bitach
Tania
T
Ijlst
Lodewijk
L
Wanders
Ronald J A
RJ
Wijburg
Frits A
FA
D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000201:enzymology; D008099:Liver / Q000196:embryology / Q000201:enzymology; D010100:Oxygen / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D005227:Fatty Acids; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D042964:Acyl-CoA Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; C044121:short-chain beta-hydroxyacyl-CoA dehydrase; D004746:Enoyl-CoA Hydratase; D005947:Glucose; D010100:Oxygen