The effect of dietary protein on the amino acid supply and threonine metabolism in the pregnant rat

Rees, William D.; Hay, Susan M.; Antipatis, Christos

doi:10.1051/rnd:2006015

Cited by 13 publications

(11 citation statements)

References 31 publications

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“…Maternal protein restriction (60 g protein/kg diet) throughout pregnancy in rats decreased maternal serum concentration of the branched chain amino acids (valine, isoleucine and leucine) by 29-36%, and the threonine concentration was reduced by 80% compared with the control group fed on 180 g protein/kg diet (Rees et al 1999). Similar results have been reported in rats showing significantly decreased maternal serum concentrations of the branched-chain amino acids and/or the total essential amino acids under maternal protein restriction (Bhasin et al 2009;Parimi et al 2004;Rees et al 2006). BeWo cells have been used to study the effects of amino acid restriction on amino acid transport (Jones et al 2006), in which DMEM Glutamax 1 was used as control, while the amino acid deprivation medium was a balanced salt solution containing no nonessential, and 50% essential amino acids used in MEM.…”

Section: Discussionsupporting

confidence: 76%

“…It has been shown that maternal low protein diet or the maternal nutrient restriction causes significant decrease in free amino acid concentrations in maternal circulation (Bhasin et al 2009;Kilberg et al 2009;Kwon et al 2004;Rees et al 2006). Branched-chain amino acids (BCAAs), particularly leucine, stimulate leptin production by rat adipocytes in vivo (Lynch et al 2006) and in vitro (Roh et al 2003).…”

Section: Introductionmentioning

confidence: 99%

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Low amino acids affect expression of 11β-HSD2 in BeWo cells through leptin-activated JAK-STAT and MAPK pathways

et al. 2011

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Maternal protein restriction diminishes placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity and causes fetal growth restriction in mammals. However, it is unknown whether such effect was caused directly by nutrient deficiency, or indirectly through the mediation of maternal hormones. In the present study, a human placental cell line (BeWo) was cultured in F12K as control and F12 as low amino acids (LAA) media for 48 h to investigate the effects of amino acids deficiency on 11β-HSD2 expression and activity. Despite a significant up-regulation of 11β-HSD2 mRNA expression in LAA cells, 11β-HSD2 activity and protein content were decreased by 38 and 54%, respectively (P<0.05), indicating a mechanism of post-transcriptional regulation. Among 5 miRNAs targeting 11β-HSD2, miR-498 was expressed significantly higher in LAA cells. Leptin concentration was significantly lower (P<0.01) in LAA medium. The mRNA expression of both isoforms of leptin receptor was significantly higher in LAA cells, although no difference was detected at protein level. To further clarify whether leptin is involved in mediating the effect of LAA on 11β-HSD2 activity, leptin was supplemented to LAA medium, whereas three specific inhibitors of leptin signaling pathways, WP1066 for JAK-STAT, PD98059 for MAPK and LY294002 for PI3K, respectively were added to control medium. Leptin restored the diminished 11β-HSD2 activity in LAA cells, whereas WP1066 (5 nM) and PD98059 (50 nM) significantly decreased 11β-HSD2 activity in control cells. In conclusion, the present results indicate that LAA diminishes 11β-HSD2 expression and activity in BeWo cells through leptin-activated JAK-STAT and MAPK pathways.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Low amino acids affect expression of 11β-HSD2 in BeWo cells through leptin-activated JAK-STAT and MAPK pathways

et al. 2011

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“…The significant increase in the essential AA threonine with advancing gestation was previously reported [ 19 ]. Rees et al [ 26 ] studied threonine metabolism in the pregnant rat and concluded that dietary protein induced increases in serine-threonine dehydratase activity favored conservation of this AA rather than its oxidation.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Metabolomic Profiling of Amino Acids and Lipids across Healthy Pregnancy

et al. 2015

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Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and ultimately, infant health outcomes. However, our understanding of whole body maternal and fetal metabolism during this critical life stage remains incomplete. The objective of this study is to utilize metabolomics to profile longitudinal patterns of fasting maternal metabolites among a cohort of non-diabetic, healthy pregnant women in order to advance our understanding of changes in protein and lipid concentrations across gestation, the biochemical pathways by which they are metabolized and to describe variation in maternal metabolites between ethnic groups. Among 160 pregnant women, amino acids, tricarboxylic acid (TCA) cycle intermediates, keto-bodies and non-esterified fatty acids were detected by liquid chromatography coupled with mass spectrometry, while polar lipids were detected through flow-injected mass spectrometry. The maternal plasma concentration of several essential and non-essential amino acids, long-chain polyunsaturated fatty acids, free carnitine, acetylcarnitine, phosphatidylcholines and sphingomyelins significantly decreased across pregnancy. Concentrations of several TCA intermediates increase as pregnancy progresses, as well as the keto-body β-hydroxybutyrate. Ratios of specific acylcarnitines used as indicators of metabolic pathways suggest a decreased beta-oxidation rate and increased carnitine palmitoyltransferase-1 enzyme activity with advancing gestation. Decreasing amino acid concentrations likely reflects placental uptake and tissue biosynthesis. The absence of any increase in plasma non-esterified fatty acids is unexpected in the catabolic phase of later pregnancy and may reflect enhanced placental fatty acid uptake and utilization for fetal tissue growth. While it appears that energy production through the TCA cycle increases as pregnancy progresses, decreasing patterns of free carnitine and acetylcarnitine as well as increased carnitine palmitoyltransferase-1 rate and β-hydroxybutyrate levels suggest a concomitant upregulation of ketogenesis to ensure sufficient energy supply in the fasting state. Several differences in metabolomic profiles between Hispanic and non-Hispanic women demonstrate phenotypic variations in prenatal metabolism which should be considered in future studies.

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“…In this respect, turnover of methionine in the rat is similar to turnover of other amino acids, such as threonine and serine, the oxidation of which also declines as gestation proceeds (14). These changes may be part of a conservation mechanism that accompanies a mobilization of maternal protein reserves to support the rapid growth of the fetuses during the final stages of gestation.…”

Section: Methionine Metabolism In Maternal Livermentioning

confidence: 94%

Effects of methyl-deficient diets on methionine and homocysteine metabolism in the pregnant rat

Wilson

Holtrop

Calder

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Rees WD. Effects of methyl-deficient diets on methionine and homocysteine metabolism in the pregnant rat. Am J Physiol Endocrinol Metab 302: E1531-E1540, 2012. First published March 27, 2012 doi:10.1152/ajpendo.00668.2011.-Although the importance of methyl metabolism in fetal development is well recognized, there is limited information on the dynamics of methionine flow through maternal and fetal tissues and on how this is related to circulating total homocysteine concentrations. Rates of homocysteine remethylation in maternal and fetal tissues on days 11, 19, and 21 of gestation were measured in pregnant rats fed diets with limiting or surplus amounts of folic acid and choline at two levels of methionine and then infused with L-[1-13 C, 2 H3-methyl]methionine. The rate of homocysteine remethylation was highest in maternal liver and declined as gestation progressed. Diets deficient in folic acid and choline reduced the production of methionine from homocysteine in maternal liver only in the animals fed a methionine-limited diet. Throughout gestation, the pancreas exported homocysteine for methylation within other tissues. Little or no methionine cycle activity was detected in the placenta at days 19 and 21 of gestation, but, during this period, fetal tissues, especially the liver, synthesized methionine from homocysteine. Greater enrichment of homocysteine in maternal plasma than placenta, even in animals fed the most-deficient diets, shows that the placenta did not contribute homocysteine to maternal plasma. Methionine synthesis from homocysteine in fetal tissues was maintained or increased when the dams were fed folate-and choline-deficient methionine-restricted diets. This study shows that methyl-deficient diets decrease the remethylation of homocysteine within maternal tissues but that these rates are protected to some extent within fetal tissues.folate; choline; fetal development; stable isotopes NUMEROUS LARGE-SCALE CLINICAL trials have clearly established the value of folic acid supplements in pregnancy (23). In addition to a marked reduction in the frequency of neural tube defects and other congenital malformations of the fetus (7, 13), improved folate status is also associated with enhanced fetal growth (17). Elevated plasma total (t-) homocysteine concentration, a marker of changes in methyl metabolism, is also recognized as a risk factor for a number of adverse pregnancy outcomes in humans (11,24,27). It has been suggested that folate supplements improve fetal development by increasing the recycling of homocysteine to methionine through the methionine cycle (Fig. 1) (1, 2, 8).The relationship between the availability of folic acid and associated methyl donors in the maternal diet and the flow through the methionine cycle in the tissues of the mother and the developing fetus is poorly quantified. Studies of pregnant rats show that methyl-deficient diets low in folic acid, choline, and methionine increase t-homocysteine concentrations in maternal and fetal plasma (9). While the enzymes of the methionin...

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The effect of dietary protein on the amino acid supply and threonine metabolism in the pregnant rat

Cited by 13 publications

References 31 publications

Low amino acids affect expression of 11β-HSD2 in BeWo cells through leptin-activated JAK-STAT and MAPK pathways

Low amino acids affect expression of 11β-HSD2 in BeWo cells through leptin-activated JAK-STAT and MAPK pathways

Longitudinal Metabolomic Profiling of Amino Acids and Lipids across Healthy Pregnancy

Effects of methyl-deficient diets on methionine and homocysteine metabolism in the pregnant rat

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