Changes in surfactant phospholipids in fetal rat lungs from normal and diabetic pregnancies

The purposes of this study were to adapt and evaluate further a pulmonary surfactant isolation method applicable to unperfused fetal rat lung, to quantitate key phospholipids phosphatidylcholine (disaturated phosphatidylcholine, and phosphatidylglycerol) of the isolated material during the last 3 days of gestation, and to determine if abnormalities in surfactant phospholipids were present in fetuses of diabetic pregnancies. A simplified scheme of sucrose gradient centrifugation proved useful for small scale preparations of material enriched in the phospholipids most characteristic of pulmonary surfactant. It was shown that fetal blood phospholipids did not contaminate the surfactant fraction and therefore would not produce artifacts in assessment of lung maturational changes. Analyses of subcellular fractions isolated at 19.5, 20.5, and 21.5 days revealed that the percentages of disaturated phosphatidylcholine relative to total phospholipids were 23-44% in the surfactant preparations and 14-21% in the residual (nonsurfactant) fractions, while the disaturated phosphatidylcholine/phosphatidylcholine ratios were 0.62 +/- 0.06 and 0.41 +/- 0.03, respectively. Summation of the amounts of individual phospholipids in the two fractions yielded data that were nearly identical to the concentrations of these compounds in whole fetal lung samples analyzed independently, implying that losses during the surfactant isolation technique were negligible. The concentrations of phosphatidylcholine, disaturated phosphatidylcholine, phosphatidylglycerol, and total phospholipids increase markedly (more than 10-fold) and progressively in surfactant fractions prepared from normal fetal rat lung at 19.5, 20.5, and 21.5 days of gestation. In contrast, the residual fractions showed no changes from 19.5 to 20.5 days and then relatively modest increases from 20.5 to 21.5 days, except for phosphatidylglycerol, which increased markedly.(ABSTRACT TRUNCATED AT 250 WORDS)     

盐酸氨溴索和地塞米松对胎鼠肺表面活性蛋白基因表达的影响

目的　探讨盐酸氨溴索和地塞米松对发育期胎鼠肺表面活性蛋白 (SPs)基因表达的影响。方法　将胎鼠 4 2只随机分为生理盐水对照组和盐酸氨溴索、地塞米松两个干预组 ,剖宫取孕19d的胎鼠肺组织作为早产鼠肺模型 ,用原位杂交研究胎鼠肺泡Ⅱ型上皮细胞内SP B基因的表达 ,逆转录PCR(RT PCR)观察分析各组肺表面活性蛋白SP A、SP B和SP CmRNA表达变化 ,用 β actinmRNA扩增产物为内参照密度扫描半定量分析。结果　 (1)发育 19d的胎鼠肺泡Ⅱ型上皮细胞内SP BmRNA表达阳性 ;(2 )鼠胚胎发育后期 ,支气管周围也分布着肺泡Ⅱ型上皮细胞 ;(3)生理盐水对照组SP A、SP B、SP CmRNA表达与 β actinmRNA比值分别为 0 81± 0 2 6、0 97± 0 2 0、0 88± 0 11。盐酸氨溴索干预SP A、SP B、SP CmRNA表达比值分别为 1 0 4± 0 16、1 2 8± 0 2 9、1 0 9± 0 2 5 ,与对照组比较显著性增加 (P <0 0 5 )。地塞米松干预后的胎鼠肺SP A、SP B、SP CmRNA表达比值分别为 1 0 8±0 2 5、1 2 3± 0 35、1 2 1± 0 2 5 ,与对照组比较显著性增加 (P <0 0 5 )。 (4 )对比盐酸氨溴索与地塞米松在促进SP A、SP B、SP C基因表达上 ,两者差异没有显著意义 (P >0 0 5 )。结论　盐酸氨溴索和地塞米松产前用药对发育期的胎鼠SPs基     

Effect of dexamethasone on pulmonary surfactant metabolism in hyperoxia-treated rat lungs

We have examined the effect of dexamethasone on the metabolism of pulmonary surfactant in normal and hyperoxia-treated rats. The relative abundance of the surfactant-specific apoprotein A (SP-A) mRNA in lung tissues and the contents of disaturated phosphatidylcholine (DSPC) and SP-A were measured in bronchoalveolar lavage fluids and in lung tissues in 4-wk-old rats exposed to room air or greater than 90% oxygen for 7 d with or without simultaneous treatment with dexamethasone (0.5 mg/kg body wt for 7 d). The relative abundance of the SP-A mRNA was marginally increased by hyperoxia (1.3-fold over controls). Dexamethasone increased the relative abundance of the SP-A mRNA to a level comparable to that with hyperoxia treatment (1.5-fold over controls). In lavage fluids, the contents of DSPC and SP-A were increased by 4- and 6-fold over controls by hyperoxia, respectively, but they were increased only by 2-fold by dexamethasone. In lung tissues, the contents of DSPC and SP-A were increased by 3- and 2-fold over controls by hyperoxia, respectively. These values in lung tissues in the air-exposed rats were not significantly increased by dexamethasone. In hyperoxia-treated rats, dexamethasone did not significantly affect the relative abundance of the SP-A mRNA level and the contents of DSPC and SP-A in lavage fluids and lung tissues. These results indicate that mechanisms other than increased synthesis of SP-A are involved in hyperoxia-induced SP-A accumulation and that dexamethasone does not affect the abnormal accumulation of pulmonary surfactant induced by hyperoxia.     

内皮素与胎肺发育及新生儿持续性肺动脉高压

内皮素 (ｅｎｄｏｔｈｅｌｉｎ ,ＥＴ)是迄今所发现的作用最强的内源性血管收缩肽 ,在心血管、肺、肾、肝、脑等脏器的疾病发生中 ,组织或血浆ＥＴ浓度有不同程度升高 ,ＥＴ在许多疾病发生中的作用日渐受到重视。肺是内皮素含量最丰富的器官 ,也是内皮素合成、代谢的主要场所。ＥＴ对气道平滑肌细胞、上皮细胞、肺血管平滑肌细胞、肺泡上皮细胞、成纤维细胞的功能活动均有调控作用。本文对ＥＴ 1在胎肺发育及新生儿持续性肺动脉高压 (ＰＰＨＮ)中的作用作一综述。1　内皮素及其受体在肺内分布　　ＥＴ由Ｙａｎａｇｉｓａｗａ在 1988年分离、…     

Effect of dexamethasone on antioxidant enzymes in fetal rat lungs and kidneys.

To determine if an enhancement in the fetal antioxidant enzyme (AOE) system by maternal dexamethasone (DEX) is specific to organ and dose, the lung and kidney of pups, whose mother received DEX (0.2 or 2 mg/kg) twice, were obtained on days 19 and 20 of gestation. Low-dose DEX increased the four AOE in the day-19 lung, but not in day-20 lung. High-dose DEX decreased the copper-zinc superoxide dismutase (SOD) and glutathione peroxidase in the lungs. Thus, the DEX-induced maturation of lung AOE is dependent on dose and timing. DEX enhanced the four AOE in the day-19 kidney at both doses. In the day-20 kidney, DEX enhanced the manganese SOD at the low dose and also catalase at the high dose, suggesting that DEX accelerates the maturation of kidney AOE as well.     

Gestational age-dependent changes in plasma inositol levels and surfactant composition in the fetal rat

To study the possibility that changes in fetal surfactant composition depend on the availability of inositol, we isolated surfactant material from lungs of fetal and neonatal rats and estimated their plasma inositol concentration. During the 18- to 22-day gestational period the amount of surfactant increases from 0.17 to 3.10 mumol phospholipids/g wet lung. From day 20 onward, 70% or more of the phospholipids is phosphatidylcholine. In this period the relatively high percentage of phosphatidylinositol (8%) in the lung surfactant decreases to 4% whereas the percentage of phosphatidylglycerol increases from 2 to 8% at parturition. During gestation the phospholipid/protein ratio of the surfactant material increase from 3 to 11 and the highest ratio is found immediately after birth. It decreases again 24 h after birth to values characteristic for surfactant from adult rats. The plasma inositol concentration drops during the 18- to 22-day period from 0.81 to 0.26 mmol/liter and a similar decrease in inositol concentration occurs in amniotic fluids. The phosphatidylglycerol/phosphatidylinositol ratio of surfactant correlated negatively with the fetal plasma inositol concentration. It is most likely that the reduction in the level of fetal plasma inositol resulting from a declining production and an increasing metabolism, causes the decrease in phosphatidylinositol and increase in PG content of the surfactant of the fetal rat.     

Effects of maternal protein-calorie malnutrition on the phospholipid composition of surfactant isolated from fetal and neonatal rat lungs. Compensation by inositol and lipid supplementation.

The effects of a maternal protein-calorie malnutrition during gestation and lactation were analyzed on fetal and postnatal lung growth and maturation, including a surfactant fraction isolated from lung tissue. There was a considerable reduction in body weight and in wet and dry lung weights of malnourished pups. Lung protein and DNA concentrations were similar in both groups except in late gestation (lung hyperplasia) and 2 and 15 d after delivery (hypocellularity). Lung glycogen breakdown was slowed down in malnourished newborns. Surfactant material was decreased the most perinatally and the reduction was more marked than for the nonsurfactant fraction of the lung. Disaturated phosphatidylcholine, the major surface active surfactant component, was decreased the most at birth (1.70 +/- 0.31 nmol/mg wet wt versus 3.68 +/- 0.17 nmol/mg in controls, n = 8) and on d 2 (5.04 +/- 0.53 nmol/mg versus 7.67 +/- 0.44 nmol/mg in controls, n = 8). There was an apparent recovery in the composition of surfactant in malnourished rats 5 d after delivery, due in fact to a decrease in controls, and an actual return to normal levels 15 to 20 d after birth. Postnatal lipid supplementation with Intralipid led to partial recovery on d 10. Inositol supplementation totally reverted the effects of malnutrition on surfactant phospholipids (8.36 +/- 0.94 nmol disaturated phosphatidylcholine/mg wet wt on d 2 versus 7.67 +/- 0.44 nmol/mg in controls and 5.55 +/- 0.62 nmol/mg in untreated malnourished rats, n = 10; 2.43 +/- 0.32 nmol disaturated phosphatidylcholine/mg wet wt on d 10 versus 3.26 +/- 0.32 nmol/mg in controls and 1.18 +/- 0.27 nmol/mg in untreated malnourished rats, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lipopolysaccharide exposure modifies high tidal volume ventilation-induced proinflammatory mediator expression in newborn rat lungs

Infection/inflammation and mechanical ventilation have both independently been shown to increase cytokine/chemokine levels in lung tissue and blood samples of premature patients. Little is known about the combined effect of systemic inflammation and mechanical ventilation on cytokine expression in the lung. We tested whether pre-existing inflammation induced by lipopolysaccharide (LPS) exposure would modify cytokine/chemokine response in newborn rat lungs to high tidal volume ventilation (HTVV). Newborn rats were randomly assigned to four groups: groups I and II (saline); groups III and IV: 3 mg/kg LPS. Groups II and IV were 24h later subjected to 3h of ventilation with a tidal volume of 25 mL/kg. HTVV alone increased IL-1beta, IL-6 and the chemokine (C-X-C motif) ligand 2 (CXCL2) mRNA expression. Although the cytokine response to LPS alone had disappeared after 24 h, the combination of LPS pretreatment and HTVV significantly increased the expression of IL-6 and IL-1beta mRNA when compared with HTVV alone. TNF-alpha expression was increased neither by HTVV alone nor in combination with LPS. IL-6 protein content in bronchoalveolar lavage increased due to the combined treatment. Thus, a subtle pre-existing inflammation combined with HTVV amplifies the proinflammatory cytokine/chemokine expression in the newborn rat lung compared with HTVV alone.     

Dexamethasone stimulation of fetal rat lung antioxidant enzyme activity in parallel with surfactant stimulation

It has recently been determined that fetal lung antioxidant enzyme activity markedly increases late in gestation. A test was made of whether this normal late-in-gestation change in O2-protective enzymes would be responsive to the maturing effect of hormonal (glucocorticoid) treatment. Pregnant rats received 0.2 mg/kg of dexamethasone (or saline) at 48 and 24 hours prior to delivery of their fetuses on gestational days 19, 20, 21, and 22 (newborn). Lung disaturated phosphatidylcholine showed an expected response to prenatal dexamethasone exposure with significant elevations of surfactant lipid at gestational days 20 and 21. A similar effect of prenatal dexamethasone treatment on the lung antioxidant defensive system was found. Superoxide dismutase, catalase, and glutathione peroxidase--enzymes protective against hyperoxia-induced lung injury--showed an accelerated pattern of maturation with significant increases in the dexamethasone-treated fetal lungs compared with control fetal lung enzyme levels at gestational days 20 and 21. The results suggest that prenatal dexamethasone treatment may have dual benefits when used in impending premature deliveries--that is, it may stimulate maturation of both the surfactant system and also the antioxidant enzyme system, and this maturation can help protect the premature newborn's lungs from the toxic complications of hyperoxic therapy that may be required because of immaturity.     

Mechanical ventilation effect on surfactant content, function, and lung compliance in the newborn rat

Studies of ventilator-associated lung injury in adult experimental animal models have documented that high tidal volume (TV) results in lung injury characterized by impaired compliance and dysfunctional surfactant. Yet, there is evidence that, in neonates, ventilation with a higher than physiologic TV leads to improved lung compliance. The purpose of our study was to evaluate how lung compliance and surfactant was altered by high TV ventilation in the neonate. We utilized a new model (mechanically air-ventilated newborn rats, 4-8 d old), and used 40 or 10 mL/kg TV strategies. Age-matched nonventilated animals served as controls. In all animals, dynamic compliance progressively increased after initiation of mechanical ventilation and was significantly greater than basal values after 60 min (p < 0.01). Lung lavage total surfactant with both TV strategies (p < 0.05) and the large aggregate fraction (only in TV = 40 mL/kg; p < 0.01) were significantly increased by 60 min of mechanical ventilation, compared with control animals. Ventilation with 40 mL/kg TV for 60 min adversely affected the lung surfactant surface-tension lowering properties (p < 0.01). After 180 min of ventilation with 40 mL/kg TV, the lung total surfactant content and dynamic compliance values were no longer distinct from the nonventilated animals' values. We conclude that, in the newborn rat, mechanical ventilation with a higher than physiologic TV increases alveolar surfactant content and, over time, alters its biophysical properties, thus promoting an initial but transient improvement in lung compliance.     

Biochemical maturation of fetal rat lung: a comprehensive study including surfactant determination

The paper describes a comprehensive assessment of lung growth and biochemical maturation in the fetal and early postnatal rat. Fetal lung grew faster than whole body between gestational day 16.5 and term. Cell number increased quasi-exponentially, except for a slowing of cell growth between days 19.5 and 20.5 of gestation. By contrast, growth was limited during the two first postnatal days. Percentage of dry tissue and protein concentration increased in parallel during the whole period. Increases in whole lung tissue phosphatidylcholine were greatest between 20.5 and 21.5 days of gestation, whereas in isolated surfactant fraction, changes were most marked between 19.5 and 20.5 days. The most striking changes were a 19-fold increase in phosphatidylcholine and a 12.5-fold increase in the total phospholipid concentrations in the surfactant fraction between gestational day 19.5 and 1 day postpartum. Similar changes occurred in disaturated phosphatidylcholine (DSPC) concentration. During the same period, phospholipids of the residual (nonsurfactant) fraction increased only about 2-fold. These data indicate that analysis of an isolated surfactant fraction is advantageous in providing a very sensitive index of augmented phospholipid production during the process of fetal lung maturation. Evidence of biochemical maturation was detected earlier in females than in males, as indicated by a significantly larger surfactant fraction DSPC concentration in 19.5-day-old females; however, this difference was modest in degree and very transient, since it was no longer demonstrable in later stages.     

Carotid baroreceptors in fetal and newborn sheep

The responses of single carotid baroreceptor afferents were determined in anaesthetized fetal lambs at 88-113 and 131-144 days gestation, and in newborn lambs 1-8 and 30-40 days old. The baroreceptors discharged in synchrony with the arterial pressure pulse and increased their discharge rate as pressure was raised by compression of the abdominal aorta. When step increases in pressure were applied to the vascularly isolated carotid sinus, baroreceptor discharge increased abruptly and then showed adaptation to a steady state level. Basal mean arterial pressure increased from 49.1 in the young fetuses to 87.5 mm Hg in the 30- to 40-day-old lambs without an accompanying increase in basal baroreceptor discharge expressed absolutely or as a function of maximum discharge for each unit. The slope of the steep portion of the stimulus-response curve decreased with gestational age from 7.89 +/- 1.57 (mean +/- SE) at 88-113 days gestation to 1.82 +/- 0.37% nerve activity.mm Hg-1 in the 30- to 49-day-old lambs. Dynamic and steady state response curves were determined using step increases in carotid sinus pressure in two fetal lambs of 135 days gestation and two lambs 8 days old. Both the dynamic and the steady state curves were less steep in the older lambs. We conclude that the sensitivity of the carotid baroreceptors is reset as arterial pressure increases throughout the last third of gestation and the first postnatal month. This resetting is seen as a shift to the right of the response curve and a decrease in its slope.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal metabolism in fetal and newborn sheep

The substrate and oxygen uptake by some organs in intact developing animals has been described, however, the kidney has not been studied. To examine substrate and oxygen uptake by the kidney, we implanted polyvinyl catheters into the renal vein, descending aorta, inferior vena cava, and urinary bladder of 11 fetal sheep (120-125 days gestation) and eight newborn lambs (1 day postnatal). Four days after surgery, blood samples were obtained simultaneously from the renal vein, aorta, and inferior vena cava for determination of oxygen content and saturation, and glucose and lactate concentrations. Renal blood flow was determined by the radionuclide-labeled microsphere method in the fetal lambs and by measuring 14C-inulin clearance in the newborn lambs. The fetal and newborn kidneys consumed oxygen at rates of 123 +/- 16 and 785 +/- 79 mumol/min/100 g kidney weight (mean +/- SEM), respectively. The increase in oxygen consumption from the fetal to the newborn period was accompanied by an increase in oxygen extraction from 25-35%, a large increase in oxygen delivery from 418 +/- 38 to 2231 +/- 127 mumol/min/100 g, and marked increases in glomerular filtration rate and sodium reabsorption (measured in six additional fetal sheep and the eight newborn lambs). This suggests that the postnatal increase in renal tubular activity is associated with an increase in oxygen consumption. Lactate was taken up by both fetal and newborn kidneys, and in nine of the 11 fetuses and in four of the eight newborns, there was net glucose release from the kidney.     

5'-Nucleotidase activity in adult and fetal rabbit lungs

5'-Nucleotidase was assayed in the membrane fractions isolated from rabbit lung homogenate. The enzyme activity was measured from the rate of hydrolysis of [U-14C]cytidine 5'-monophosphate (CMP). The optimal pH of the rate of hydrolysis is around 8.0 and the enzyme activity is stimulated by Mg2+. The apparent Km and Vmax of the enzyme in the microsomal fraction for CMP were 3.33 mM and 1.43 mumol/min/mg protein, respectively. During lung development the enzyme activity increased moderately at late gestational ages and reached its maximum level in adults (p less than 0.001). The developing profile of 5'-nucleotidase activity is similar to the developing pattern of the CMP content in rabbit lungs.     

Factors influencing surfactant composition in the newborn infant

In order to evaluate the surfactant maturation of the neonate, tracheal aspirates were analyzed in 84 newborn infants within 12 h of birth. Using 2-dimensional thin-layer chromatography, 9 different phospholipids were identified. Dynamic surface tension measurements were performed with a modified Wilhelmy balance. Five different groups of infants with typical phospholipid patterns were characterized: i.e., 1. Normal term newborn. 2. RDS in the preterm infant. 3. Acceleration of lung maturity in preterm infants without RDS. 4. Retardation in term infants with RDS. 5. Therapeutic induction of pulmonary maturity in preterm infants following maternal glucocorticoid administration.Mature lung effluent contains high concentrations of phosphatidylcholine (PC) and phosphatidylglycerol (PG). In infants with RDS, PC is low and PG absent. Accelerated lung maturity was observed after chronic prenatal stress, such as prolonged rupture of the membranes, chronic vaginal bleeding, and maternal hepatitis or drug addiction. Retardation of pulmonary maturity was seen in infants with alpha-1-AT-deficiency, maternal diabetes and maternal hypothyroidism. Administration of methylprednisolone to the mother 24 h to 72 h before birth induced both the synthesis of PC and PG in the preterm infants, resulting in an almost full-term phospholipid pattern as early as 31 weeks of gestation. The significance of these factors on the pathogenesis of RDS is discussed.Dedicated to Prof. Dr. H. Bickel on occasion of his 60th birthday     

Hoxa5基因在先天性膈疝大鼠模型胎肺中的表达

目的 研究Hoxa5基因在先天性膈疝(congenital diaphragmatic hernia,CDH)胎肺中的表达特点以及探讨其在CDH肺发育不良发生机制中的可能作用.方法 采用实时荧光定量PCR(real time quantitative PCR,QPCR)方法检测Hoxa5基因在妊娠第17.5天、19.5天、21.5天的nitrofen诱导CDH大鼠模型胎肺及正常对照大鼠胎肺巾的相对表达量.结果 正常对照组胎肺中Hoxa5 mRNA的表达水平随着胎龄的增加旱下降趋势,其中第21.5天胎肺中Hoxa5 mRNA的表达水平显著下降,与其他二胎龄点相比差异有统计学意义(P＜0.05);CDH组中Hoxa5 mRNA的表达趋势与正常胎肺相似,即随胎龄的增加其表达量下降,其当中第21.5天胎肺中Hoxa5 mRNA的表达水平明显降低,与其他二胎龄点相比差异有统计学意义(P＜0.05).第17.5天与19.5天胎龄CDH组胎肺中Hoxa5 mRNA的表达水平分别与相应对照组相比,差异无统计学意义;而妊娠晚期(第21.5天胎龄)CDH组胎肺中Hoxa5 mRNA的表达水平高于对照组.差异具有统计学意义.结论 正常对照组中第21.5天胎龄时Hoxa5 mRNA的表达水平显著降低,提示Hoxa5 mRNA在孕晚期的低表达是正常肺发育的分子基础之一;而CDH组中第21.5天胎龄时Hoxa5 mRNA的表达水平明显高于对照组,提示Hoxa5在孕晚期CDH胎肺中Hoxa5的高表达可能是CDH肺发育不良形成机制之一.     

Association of changes in bombesin immunoreactive neuroendocrine cells in lungs of newborn infants with persistent fetal circulation and brainstem damage due to birth asphyxia

The pulmonary neuroendocrine (NE) cells, from 16 term infants dying at 1-4 days of age from birth asphyxia, were immuno stained for bombesin-like immunoreactivity by the immunoperoxidase method. The distribution and frequency of bombesin-immunoreactive NE cells were quantified morphometrically and correlated with the presence or absence of brainstem function and persistent fetal circulation (PFC). In infants with loss of brainstem function, the frequency of bombesin immunoreactive NE cells was significantly increased compared to infants with intact brainstem function, i.e. meconium aspiration with PFC. Infants with brainstem injury, with one exception, failed to develop PFC. Pathological changes in the tegmentum of the brainstem, i.e. containing the respiratory center, correlated in nine of 10 cases with loss of brainstem function. These data suggest an inverse relationship between brainstem function, release of bombesin-like peptide from the pulmonary NE cells and the functional state of the pulmonary vasculature. Intact brainstem function appears to be essential for both the release of bombesin-like peptide from the NE cells and for pulmonary vasoconstriction leading to PFC; absence of brainstem function is, on the other hand, associated with failure to release bombesin-like peptide and loss of PFC type reactivity in the pulmonary vasculature. However, it appears unlikely that bombesin itself is a direct mediator of pulmonary vasoconstriction.     

Lipoproteins and apoproteins of fetal and newborn piglets

Serum lipids, very low in the fetus and at birth, increased rapidly after the first feeding. Cholesterol was mainly in the free form. Esterified cholesterol rose rapidly, but free cholesterol remained in high proportions (30%) until after weaning. Very high phospholipid concentrations show that triglycerides are not the only major product of esterification and suggest a possible use for energetic purposes. Fetal lipoproteins had a general pattern similar to that of adults, but high-density lipoproteins (HDL) were denser (1.128 g/ml) and correspondingly richer in proteins. The presence of apoprotein AI and of the light intestinal form of apoprotein B in the triglyceride-rich fractions as well as that of apoprotein AIV in HDL was indicative of an early contribution of enterocytes to the lipoprotein pool. Low-density lipoprotein apoproteins were heterogeneous until 14 days, as they are in the human fetus, and contained, besides apoprotein B, all the main apoproteins, HDL reached concentrations of 400 mg/100 ml at 3 and 4 weeks of age, above 3-fold higher than those of chow-fed adults, but also 1.5-fold higher than those of growing pigs fed a 20% fat diet, thereby showing a high capacity of the very young animal to synthesize HDL and apoprotein AI in particular. The many similarities with the evolution of lipoprotein in the newborn human validate the young pig as a model in the study of perinatal nutrition.