Evidence for Fatty Acid Oxidation in Human Placenta, and the Relationship of Fatty Acid Oxidation Enzyme Activities with Gestational Age

Rakheja, Dinesh; Bennett, Michael J.; Foster, Barbara; Domiati‐Saad, Rana; Rogers, Beverly Barton

doi:10.1053/plac.2002.0808

Cited by 77 publications

(51 citation statements)

References 32 publications

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“…Recent studies in human placenta already demonstrated a remarkable high activity of FAO enzymes (20 -22). In placenta, the activity of the enzymes LCHAD and short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) were inversely correlated with gestational age (20). Furthermore, the activity of CPT2 and of VLCAD was higher in term human placenta than in adult human liver (21).…”

Section: Discussionmentioning

confidence: 99%

Long-Chain Fatty Acid Oxidation during Early Human Development

et al. 2005

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Patients with very long-chain acyl-CoA dehydrogenase (VLCAD) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)/mitochondrial trifunctional protein (MTP) deficiency, disorders of the mitochondrial long-chain fatty acid oxidation, can present with hypoketotic hypoglycemia, rhabdomyolysis, and cardiomyopathy. In addition, patients with LCHAD/MTP deficiency may suffer from retinopathy and peripheral neuropathy. Until recently, there was no indication of intrauterine morbidity in these disorders. This observation was in line with the widely accepted view that fatty acid oxidation (FAO) does not play a significant role during fetal life. However, the high incidence of the gestational complications acute fatty liver of pregnancy and hemolysis, elevated liver enzymes, and low platelets syndrome observed in mothers carrying a LCHAD/MTP-deficient child and the recent reports of fetal hydrops due to cardiomyopathy in MTP deficiency, as well as the high incidence of intrauterine growth retardation in children with LCHAD/MTP deficiency, suggest that FAO may play an important role during fetal development. In this study, using in situ hybridization of the VLCAD and the LCHAD mRNA, we report on the expression of genes involved in the mitochondrial oxidation of long-chain fatty acids during early human development. Furthermore, we measured the enzymatic activity of the VLCAD, LCHAD, and carnitine palmitoyl-CoA transferase 2 (CPT2) enzymes in different human fetal tissues. Human embryos (at d 35 and 49 of development) and separate tissues (5-20 wk of development) were used. The results show a strong expression of VLCAD and LCHAD mRNA and a high enzymatic activity of VLCAD, LCHAD, and CPT2 in a number of tissues, such as liver and heart. In addition, high expression of LCHAD mRNA was observed in the neural retina and CNS. Mitochondrial oxidation of fatty acids plays a critical role in energy metabolism after birth. The heart preferentially uses fatty acids as a substrate for energy production. In addition, during moderately severe exercise, skeletal muscle predominantly utilizes fatty acids as an energy source. In the liver, FAO is used during fasting to produce ketone bodies that are exported from the liver and can be used for energy production by peripheral tissues such as the brain. Mitochondrial FAO of long-chain fatty acids involves the concerted action of a multitude of enzymes. This process starts with the carnitinemediated transfer of the long-chain fatty acids, activated to their CoA esters, over the mitochondrial inner-membrane. This involves the activity of three enzymes: CPT1, carnitine acylcarnitine translocase (CACT), and CPT2. Once inside the

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Section: Discussionmentioning

confidence: 99%

Long-Chain Fatty Acid Oxidation during Early Human Development

et al. 2005

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“…If b > 0, a certain amount of 13 C-fatty acid was taken up by the placenta but not delivered to the fetal circulation and thus had to be retained by by long-chain fatty acid acyl-CoA synthetase in the cytosol or, for the fatty acid transport protein family of membrane transporters, is directly associated with the membrane transport protein (13,14). Acyl-CoA can then be esterified into different lipid pools, triglycerides, phospholipids, and cholesterol esters (15,16); enter the -oxidation pathway (17,18); or be used for the biosynthesis of eicosanoids (19). Because most fatty acids are converted to Acyl-CoA in the cytosol, the fatty acid concentration would be expected to be low.…”

Section: Uptake and Delivery Mass Balancementioning

confidence: 99%

“…Glucose transferred to the placenta must somehow bypass this process because there is no placental glucose-6-phosphatese. However, the placenta does express genes for enzymes that can release fatty acids from acylCoA, triglyceride, and phospholipid pools (18,21). It has been suggested that glucose and fatty acid transfer may occur preferentially in regions of vascular syncytial membrane where diffusion distance is low and metabolism may be limited (22).…”

Section: Uptake and Delivery Mass Balancementioning

confidence: 99%

The influence of placental metabolism on fatty acid transfer to the fetus

Perazzolo

Hirschmugl

Wadsack

et al. 2017

Journal of Lipid Research

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“…Fetal carnitine is derived from the mother via transplacental transfer of carnitine (13). The Na ϩ -dependent high-affinity carnitine transporter OCTN2 (14,15) is expressed in human placenta (16), and placental OCTN2 is necessary for the accumulation of carnitine in placenta and fetus, and, consequently, for the oxidation of long-chain fatty acids in fetal-placental unit (17,18). Studies on OCTN2 -/-mice suggest that the placental carnitine synthesis might depend on the carnitine status of the fetus and/or the mother (13).…”

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confidence: 99%

Determination of Carnitine Ester Patterns During the Second Half of Pregnancy, at Delivery, and in Neonatal Cord Blood by Tandem Mass Spectrometry: Complex and Dynamic Involvement of Carnitine in the Intermediary Metabolism

et al. 2007

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ABSTRACT:We studied plasma concentrations of free carnitine and 30 carnitine esters by electron spray ionization (ESI) tandem mass spectrometry in 37 pregnant women at the 20th and 30th weeks of gestation and at delivery, and in their neonates at birth, and in 22 age-matched nonpregnant women. The plasma levels of acetylcarnitine and carnitine esters with more than five carbons were significantly higher, whereas the concentration of free carnitine was significantly lower at term than at the 20th week of pregnancy (16.75 Ϯ 0.89 versus 19.61 Ϯ 1.25). Almost all of C2-to C12-carnitine esters were significantly lower, whereas C16-and C18-carnitines with in-chain modifications were significantly higher in mothers at delivery compared with nonpregnant women. Plasma levels of free carnitine and C2-, C3-, C4-, C5-, C6-, and C16-carnitines were significantly lower, while concentrations of carnitine esters with 8, 10, 12 and 18 carbons in the acyl chain as well as C14:1-, C14:2-, and C16:1-OH-carnitines were significantly higher in mothers at term than in their neonates. The data of the present study clearly show dynamic features of plasma carnitine profile during pregnancy and indicate an extraordinarily active participation of the carnitine in the intermediary metabolism both in the pregnant woman and in the neonate. (Pediatr Res 62: 88-92, 2007) D uring the first two trimesters of pregnancy, the maternal metabolism continuously adapts, with accretion of fat stores deriving from aliments and then shifting to an accelerated catabolism of lipids in the late gestation (1). In human newborns, fat represents 15-16% of total body composition, and the accumulation of white adipose tissue occurs predominantly during the last trimester (2).Carnitine is a conditionally essential quaternary amino acid that plays a crucial role in beta-oxidation of long-chain fatty acids and in ketogenesis (3-5). The carnitine molecule can form esters with FFA of different chain length; the endogenous (4) or exogenous acyl groups (6 -8) are transferred from coenzyme-A to carnitine by different carnitine acyltransferases (9).Availability of carnitine has been reported to be essential for the developing fetus (10,11), and carnitine is stored in increasing amounts in fetal tissues, mainly in the liver and muscle, during the last period of gestation (12). Fetal carnitine is derived from the mother via transplacental transfer of carnitine (13). The Na ϩ -dependent high-affinity carnitine transporter OCTN2 (14,15) is expressed in human placenta (16), and placental OCTN2 is necessary for the accumulation of carnitine in placenta and fetus, and, consequently, for the oxidation of long-chain fatty acids in fetal-placental unit (17,18). Studies on OCTN2 -/-mice suggest that the placental carnitine synthesis might depend on the carnitine status of the fetus and/or the mother (13). On the basis of these observations, it is clear that further studies of maternal and neonatal carnitine status are needed, including the investigation of participation of carnitine ...

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Evidence for Fatty Acid Oxidation in Human Placenta, and the Relationship of Fatty Acid Oxidation Enzyme Activities with Gestational Age

Cited by 77 publications

References 32 publications

Long-Chain Fatty Acid Oxidation during Early Human Development

Long-Chain Fatty Acid Oxidation during Early Human Development

The influence of placental metabolism on fatty acid transfer to the fetus

Determination of Carnitine Ester Patterns During the Second Half of Pregnancy, at Delivery, and in Neonatal Cord Blood by Tandem Mass Spectrometry: Complex and Dynamic Involvement of Carnitine in the Intermediary Metabolism

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