Aromatic amino acids are utilized and protein synthesis is stimulated during amino acid infusion in the ovine fetus.

The purpose of this study was to determine whether the ovine fetus is capable of increased disposal of an amino acid load; if so, would it respond by increased protein synthesis, amino acid catabolism or both? A further purpose of the study was to determine whether the pathways of aromatic amino acid catabolism are functional in the fetus. Late gestation ovine fetuses of well-nourished ewes received an infusion of Aminosyn PF alone (APF), and Aminosyn PF + glycyl-L-tyrosine (APF+GT) at rates estimated to double the intake of these amino acids. The initial study, using APF, was performed at 126 +/- 1.4 d; the APF+GT study was performed at 132 +/- 1.7 d (term = 150 d). Phenylalanine and tyrosine kinetics were determined using both stable and radioactive isotopes. Plasma concentrations of most amino acids, but not tyrosine, increased during both studies; tyrosine concentration increased only during the APF+GT study. Phenylalanine rate of appearance and phenylalanine hydroxylation increased during both studies. Tyrosine rate of appearance increased only during the APF+GT study; tyrosine oxidation did not increase during either study. Fetal protein synthesis increased significantly during both studies, producing a significant increase in fetal protein accretion. Fetal proteolysis was unchanged in response to either amino acid infusion. These results indicate that the fetus responds to an acute increase in amino acid supply primarily by increasing protein synthesis and accretion, with a smaller but significant increase in amino acid catabolism also. Both phenylalanine hydroxylation and tyrosine oxidation are active in the fetus, and the fetus is able to increase phenylalanine hydroxylation rapidly in response to increased supply.     

Effects of dietary mixtures of amino acids on fetal growth and maternal and fetal amino acid pools in experimental maternal phenylketonuria

BACKGROUND: Branched-chain amino acids have been reported to improve fetal brain development in a rat model in which maternal phenylketonuria (PKU) is induced by the inclusion of an inhibitor of phenylalanine hydroxylase, DL-p-chlorophenylalanine, and L-phenylalanine in the diet. OBJECTIVE: We studied whether a dietary mixture of several large neutral amino acids (LNAAs) would improve fetal brain growth and normalize the fetal brain amino acid profile in a rat model of maternal PKU induced by DL-alpha-methylphenylalanine (AMPhe). DESIGN: Long-Evans rats were fed a basal diet or a similar diet containing 0.5% AMPhe + 3.0% L-phenylalanine (AMPhe + Phe diet) from day 11 until day 20 of gestation in experiments to test various mixtures of LNAAs. Maternal weight gains and food intakes to day 20, fetal body and brain weights at day 20, and fetal brain and fetal and maternal plasma amino acid concentrations at day 20 were measured. RESULTS: Concentrations of phenylalanine and tyrosine in fetal brain and in maternal and fetal plasma were higher and fetal brain weights were lower in rats fed the AMPhe + Phe diet than in rats fed the basal diet. However, fetal brain growth was higher and concentrations of phenylalanine and tyrosine in fetal brain and in maternal and fetal plasma were lower in rats fed the AMPhe + Phe diet plus LNAAs than in rats fed the diet containing AMPhe + Phe alone. CONCLUSION: LNAA supplementation of the diet improved fetal amino acid profiles and alleviated most, but not all, of the depression in fetal brain growth observed in this model of maternal PKU.     

母体肠道菌群失调及其子宫内转移对母胎影响的研究进展

子宫内有细菌存在,并且可能对胎儿产生影响。母胎间菌群转移的具体作用机制迄今尚未阐明。胎儿肠道菌群的主要来源除了母体血液、胎盘和羊水外,母体肠道亦可能是胎儿肠道菌群的主要来源之一。母体肠道菌群通过血液等途径转移至子宫内,再经过胎盘血液循环和羊水等途径转移至胎儿肠道和免疫系统。母体孕期肠道菌群的结构与数量,可对孕妇及其子代肥胖、神经系统发育异常和血压调节产生影响。随着基因测序技术的发展,有助于更深入探讨母体肠道菌群失调及其子宫内转移与母胎疾病之间的关系,为胎源性疾病的预防和干预提供理论依据。笔者拟就母体肠道菌群失调及其子宫内转移对母胎影响的研究进展进行综述。     

The effect of dietary protein and energy restriction on heat production and growth costs in the young rat

1. The effect of dietary protein and energy restriction on heat production and growth costs has been examined in rats fed on a marginal (MP) or high (HP) protein diet, containing 9.2% or 22% respectively of the gross energy content as casein. Diets were given either ad lib. or at approximately 25, 50 or 75% of the ad lib. intake. 2. Heat production (kJ/kg body-weight (W)0.75 per d) was increased by 23% in rats fed on the MP diet ad lib., as compared with their HP controls (P less than 0.01). 3. Factorial analysis of the data showed that the overall cost of energy deposition (kJ/kJ; Ee) was elevated on the MP diet (MP 1.7, HP 1.28; P less than 0.001). Maintenance requirements (kJ/kg W0.75 per d) for zero energy balance were unchanged (MP 562, HP 573). 4. The partial energy cost of protein deposition (Ep) varied with dietary manipulation. If the partial energy cost of fat deposition (Ef) was assumed constant at 1.25 kJ/kJ, and maintenance requirements were assumed to vary with metabolic body size (W0.75), Ep was elevated on the MP diet. On both diets, Ep was reduced at low energy intakes. 5. The significance of these results is discussed in the context of current approaches to the analysis and interpretation of findings describing dietary induced changes in the rate of heat production.     

The conflicting effects of maternal nutrient restriction and early-life obesity on renal health

Epidemiological and animal studies have demonstrated that early-life nutrition alters the metabolic responses and generates structural changes in complex tissues, such as the kidneys, which may lead to a reduction in the offspring lifespan. Independently, obesity induces a spontaneous low-grade chronic inflammatory response by modulating several of the major metabolic pathways that ultimately compromise long-term renal health. However, the combined effects of maternal nutrition and early-life obesity in the development of renal diseases are far from conclusive. Previous results, using the ovine model, demonstrated that the combination of a reduction in fetal nutrition and juvenile obesity induced a series of adaptations associated with severe metabolic syndrome in the heart and adipose tissue. Surprisingly, exposure to an obesogenic environment in the kidney of those offspring produced an apparent reduction in glomerulosclerosis in relation to age- and weight-matched controls. However, this reduction in cellular apoptosis was accompanied by a rise in glomerular filtration rate and blood pressure of equal intensity when compared with obese controls. The intention of this review is to explain the adaptive responses observed in this model, based on insights into the mechanism of renal fetal programming, and their potential interactions with some of the metabolic changes produced by obesity.     

The maternal endocrine environment in the low-protein model of intra-uterine growth restriction

Many adult diseases, including type 2 diabetes, hypertension and cardiovascular disease, are related to low birth weight. The mechanistic basis of this relationship is not known. To investigate the role of fetal undernutrition, we used a rat model of maternal protein restriction in which dams were fed a diet containing 80 g protein/kg (v. 200 g/kg in the control group) throughout gestation and lactation. Offspring were born smaller than controls and in adulthood developed diabetes, hyperinsulinaemia and tissue insulin resistance. To determine possible mechanisms of fetal programming, circulating levels of several hormones were measured in maternal plasma at gestational days 14, 17 and 21 and fetal plasma at gestational day 21. Several differences were noted at day 14, when glucose concentrations in maternal and feto-placental blood were raised significantly (P=0.04 and P=0.0001 respectively); insulin levels in the low-protein (LP) dams were raised (P=0.04), prolactin levels were raised (P=0.047) and progesterone levels were reduced (P=0.02). Circulating 17beta-oestradiol in the LP dams was raised by 35 % over those of the controls from day 17 to day 21 (P=0.008). A significant decrease in maternal leptin levels (P=0.004) was observed at gestation on day 21. Neither oestradiol nor leptin levels were altered in the fetal circulation at day 21. Maternal and fetal corticosterone levels were comparable with control levels, suggesting that they do not initiate the programming effects in this model. Our present results suggest that maternal protein restriction imposes changes in maternal levels of glucose, insulin, prolactin, progesterone, oestradiol and leptin; these changes could influence the programming of eventual adult disease in the developing fetus.     

Differential effects of amino acid and ketoacid on protein metabolism in humans

We examined the effects of insulin, amino acid (AA), and branched-chain ketoacid (KA) availability on leucine kinetics in eight healthy volunteers (age = 22 +/- 2 y, body mass index = 24 +/- 1 kg) by using the euglycemic insulin clamp and [1-14C] leucine turnover techniques. Four experimental conditions were studied: study I, hyperinsulinemia; study II, hyperinsulinemia with maintenance of basal plasma AA and branched-chain KA concentrations; study III, hyperinsulinemia with hyperaminoacidemia and basal plasma branched-chain KA concentrations; and study IV, hyperinsulinemia plus basal plasma AA concentrations and elevated branched-chain KA levels. Basal endogenous leucine flux (ELF) averaged 1.20 +/- 0.05 (mumol.kg-1.min-1, mean +/- SE); basal leucine oxidation (LOX) was 0.25 +/- 0.01; and basal non-oxidative leucine disposal (NOLD) was 0.95 +/- 0.04. ELF significantly decreased in study I (0.77 +/- 0.06 mumol.kg-1.min-1, P < 0.01 versus basal). When plasma AA and branched-chain KA were either maintained at their basal levels (study II) or increased above baseline values (studies III and IV), ELF declined further (0.64 +/- 0.05, 0.66 +/- 0.02, and 0.66 +/- 0.03 mumol.kg-1.min-1, respectively; all Ps < 0.01 versus basal and P < 0.01 versus study I). LOX declined in study I (0.12 +/- 0.02 mumol.kg-1.min-1, P < 0.01 versus basal) but increased significantly in studies II, III, and IV (0.31 +/- 0.04, 0.37 +/- 0.03, and 0.40 +/- 0.03 mumol.kg-1.min-1, respectively, all Ps < 0.01 versus basal, P < 0.05 study IV versus study II, and P < 0.05 study III versus study II). NOLD declined in study I (0.65 +/- 0.05 mumol/kg.min, P < 0.01 versus basal), whereas neither the maintenance of basal plasma AA/branched-chain KA levels (study II; 0.89 +/- 0.2 mumol.kg-1.min-1) nor the elevation of plasma branched-chain KA concentration (study IV; 0.96 +/- 0.1 mumol.kg-1.min-1) increased NOLD above baseline level. A stimulation of NOLD was observed only when plasma AA levels were increased (study III; 1.23 +/- 0.03 mumol/kg.min, P < 0.01 versus basal). In conclusion, the present data do not support the concept of a direct anabolic action of ketoanalogs but do provide additional evidence for the pivotal role of AA availability in the stimulation of whole-body protein synthesis.     

The effects of prenatal protein restriction on the developing mouse cerebrum

Purified low protein maternal diets cause a reduction in total weight and protein content but not in DNA content (cell number) of the cerebrum of newborn mice. Female mice were fed diets in which 8%, 11%, 15%, or 27% (control) was casein as the sole source of protein for 1 or 2 months prior to mating and throughout gestation. A 15% casein diet fed for 1 month had no effect on brain weight, DNA content (cell number) or protein content in the cerebrums of newborn mice. Female mice fed an 8% or 11% protein diet for 1 or 2 months prior to conception and throughout gestation gave birth to young that had a decreased cerebral weight and protein content. However in neither case was the amount of cerebral DNA (cell number) of the newborn from females in the low protein group significantly different from that in the cerebrums of mice born to females on the normal protein diet.     

高蛋氨酸饲料对大鼠氨基酸代谢的影响

目的：研究高蛋氨酸饲料对大鼠生长及体内蛋白质、氨基酸代谢的影响。方法：SD大鼠20只，随机分为两组，即高蛋氨酸组（M组）和对照组（C组）各10只。M组每天给予含3％蛋氨酸的饲料，动态测量体重，分别在0、4、8、12周眼眶取血测血清氨基酸，并在12周处死动物，测肝的游离氨基酸含量。结果：高蛋氨酸在4周时，即出现高同型半胱氨酸血症、高蛋氨酸血症；12周时血清苏氨酸、缬氨酸、亮氨酸、苯丙氨酸含量明显下降，脯氨酸、 精氨酸和丙氨酸血清含量均有显著增高。肝内七种必需氨基酸含量实验组均显著高于对照组，而非必需氨基酸则实验组含量明显低于对照组。同时，实验组大鼠体重增长缓慢。结论：高蛋氨酸饲料能影响血清、肝的游离氨基酸含量，抑制大鼠生长。     

Early effects of hypervitaminosis A on gluconeogenic activity and amino acid metabolizing enzymes of rat liver.

In an earlier report from this laboratory, one of the early manifestations of hypervitaminosis A was shown to be a marked stimulation of hepatic gluconeogenesis. In the present study, effects of feeding 30,000 IU of retinyl palmitate to young rats (80-100 g), once daily, for 2 days on the incorporation of 14C-labeled precursors into glucose and glycogen by liver slices, levels of amino acids in blood and tissues, and activities of some important amino acid catabolizing enzymes in the liver were investigated. A stimulation of hepatic gluconeogenesis in hypervitaminosis A was indicated by the increased incorporation of 14C-labeled alanine and bicarbonate into glucose and glycogen by liver slices. Excessive intake of retinol caused a marked increase in the activities of hepatic alanine aminotransferase and ornithine aminotransferase and a decrease in that of tryptophan pyrrolase, without affecting those of tyrosine aminotransferase and serine dehydratase. The ratio of NADH:NAD in the livers of rats fed excess retinol was significantly increased. It is suggested that enhancement of glucoeogenesis in hypervitaminosis A is caused by a stimulation of gluconeogenic activity of the liver.