Lipoproteins and lipids in fetal, neonatal and adult rat serum

Levels of the serum lipoproteins (HDL, LDL and VLDL) and lipids in the fetal, neonatal and pregnant rat were measured using electrophoretic, immunological and biochemical methods. The results were compared to those of the adult rat. In the fetal rat at the end of gestation, the lipoprotein pattern was dominated by LDL (beta-lipoprotein). Fetal HDL (alpha-lipoprotein) occurred at a low concentration and showed a lower proportion of cholesterol and a higher proportion of triglycerides than did HDL in the adult rat serum. VLDL (pre-beta-lipoprotein) was present only at very low concentrations. The lipoprotein pattern of suckling neonatal rats showed rapidly increasing levels of VLDL and LDL, and high serum lipid values during the first 2 weeks after birth. The lipoprotein pattern of the adult rat, with the HDL fraction dominating, was completely developed by about 4 weeks after birth. In rats during late pregnancy, very high serum values were found for VLDL and LDL. High levels of triglycerides associated with these fractions were also seen. The serum lipoprotein development of the fetal and neonatal rat is different from that reported for the pig and man. This focuses the interest on the differences in lipid and lipoprotein metabolism between species during ontogenic development.     

Vitamin E status in hypercholesterolemic children

The prime role of oxidized low-density lipoprotein in the pathogenesis of atherosclerosis is almost universally accepted. Fat soluble antioxidant vitamin E associated with lipoproteins, appears to have antiatheroma properties. In the presented studies concentration of vitamin E and the relationship between tocopherol and lipids were studied in blood of hypercholesterolemic children. Level of vitamin E was determined by high-performance liquid chromatography (HPLC) method. Compared with normocholesterolemic children, hypercholesterolemic patients had a significantly lower red blood cell vitamin E content (2.55 +/- 0.19 micromol/l vs 3.15+/- 0.33 micromol/l; p<0.005) in spite of their higher plasma vitamin E concentration (27.9 +/- 8.3 micromol/l vs 21.01 +/- 3.6 micromol/l; pl;0.001). In the group of patient tocopherol-to-total cholesterol and tocopherol-to-lipids ratio was statistically lower compared to those in the control group. In hypecholesterolemic children vitamin E positively correlated with total cholesterol (r=0.43; p<0.02), LDL-C (low-density lipoprotein cholesterol) (r=0.42; p<0.02) and lipids (triglycerides + total cholesterol) (r=0.45; p<0.02). This study demonstrates that total plasma vitamin E concentration is not a suitable predictor of cell vitamin E status. Our results suggested that the tocopherol of erythrocytes and vitamin E to lipids ratio in plasma, could be more meaningful indicators to evaluate the vitamin E status in hypercholesterolemic children.     

Lipids, lipoproteins and apolipoproteins AI, AII, B, CII, CIII and E in newborns.

In this study lipid and apolipoprotein patterns were investigated at birth and compared with those of adults. In cord sera, cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were 38.2, 46.2, 50.5, and 31.9%, respectively, of adult values. Apolipoprotein AII, B and CIII were 48.6, 30.6 and 44.5% of adult values, while apo AI, apo CII and apo E showed values approaching those of adults (63.4, 73.3 and 89.7%, respectively). Also cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios were lower in newborns. In cord sera, lipids were correlated with various apolipoproteins in a surprisingly different way from adult sera. HDL cholesterol was not inversely correlated with triglycerides, and showed a highly positive correlation with apo E, apo CII and apo CIII, which did not correlate with HDL cholesterol in adults. These data supported the presence of significant differences in plasma concentrations and composition of lipoproteins at birth. Therefore HDL, apo CII, and apo E seem to play a different and more important metabolic role in neonatal lipid metabolism.     

SERUM APOLIPOPROTEINS AND LIPOPROTEIN (a) DURING THE FIRST WEEK OF LIFE

ABSTRACT. The levels of apolipoproteins, A-I, A-II, B and E, lipoprotein (a) and of total cholesterol and triglycerides were determined in cord serum and in capillary serum at the fifth day of life in a group of 44 term newborns. Additionally, cord serum lipoproteins were estimated. Sera from 26 healthy adults were studied for comparison. The concentrations of lipids and lipoproteins in cord serum were diminished as compared to adult levels. The occurrence of lipoprotein (a) in cord serum in concentrations significantly lower than in adults could be established. Serum apolipoproteins A-I, A-II and B were significantly lower at birth than in the adult, whereas apolipoprotein E levels did not differ from adult concentrations. During the first five days apolipoprotein B levels more than doubled, apolipoprotein A-I increased moderately and apolipoprotein E rose slightly. In contrast, serum lipoprotein (a) and apolipoprotein A-II did not change signiflcantly. Unlike serum cholesterol, the levels of apolipoproteins B and E at day five were significantly correlated to those measured at birth in the same infants. The changes of the apolipoprotein pattern during the first week of life reflect the evolution of the lipid transport system of the newborn and may be related to the increasing utilisation of fat and to hormonal factors.     

Serum apolipoproteins and lipoprotein (a) during the first week of life

The levels of apolipoproteins, A-I, A-II, B and E, lipoprotein (a) and of total cholesterol and triglycerides were determined in cord serum and in capillary serum at the fifth day of life in a group of 44 term newborns. Additionally, cord serum lipoproteins were estimated. Sera from 26 healthy adults were studied for comparison. The concentrations of lipids and lipoproteins in cord serum were diminished as compared to adult levels. The occurrence of lipoprotein (a) in cord serum in concentrations significantly lower than in adults could be established. Serum apolipoproteins A-I, A-II and B were significantly lower at birth than in the adult, whereas apolipoprotein E levels did not differ from adult concentrations. During the first five days apolipoprotein B levels more than doubled, apolipoprotein A-I increased moderately and apolipoprotein E rose slightly. In contrast, serum lipoprotein (a) and apolipoprotein A-II did not change significantly. Unlike serum cholesterol, the levels of apolipoproteins B and E at day five were significantly correlated to those measured at birth in the same infants. The changes of the apolipoprotein pattern during the first week of life reflect the evolution of the lipid transport system of the newborn and may be related to the increasing utilisation of fat and to hormonal factors.     

Changes in Plasma Lipoproteins from First Day to Third Week of Life in Healthy Breast-fed Infants

ABSTRACT. Plasma lipoproteins were measured in seven healthy breast-fed infants three times during the first and on the third, sixth and twenty-first days of life. Plasma total beta-lipoprotein, very low density and low density lipoprotein increased three times during the first week of life. Plasma total apolipoprotein A-I and high density lipoprotein increased twice between the first and third week of life. These dramatic changes in plasma lipoprotein concentrations during the neonatal period can best be explained by the effect of feeding.     

Changes in plasma lipoproteins from first day to third week of life in healthy breast-fed infants. I. Lipid and protein composition of lipoproteins

Plasma lipoproteins were measured in seven healthy breast-fed infants three times during the first and on the third, sixth and twenty-first days of life. Plasma total beta-lipoprotein, very low density and low density lipoprotein increased three times during the first week of life. Plasma total apolipoprotein A-I and high density lipoprotein increased twice between the first and third week of life. These dramatic changes in plasma lipoprotein concentrations during the neonatal period can best be explained by the effect of feeding.     

Effects of APOA5 S19W polymorphism on growth,insulin sensitivity and lipoproteins in normoweight neonates

Apolipoprotein (Apo) A5 is a protein involved in the activation of lipoprotein lipase (LPL) and the metabolism of triglyceride (TG)-rich lipoproteins. LPL plays a major role in the metabolism of TG-rich lipoproteins, and placental LPL activity is known to correlate positively with foetal fat deposition and size. We examine the association between the common APOA5 S19W polymorphism and neonatal anthropometrical measurements, lipoprotein and hormone concentrations, and insulin sensitivity in 58 normal weight Caucasian newborns from the Mérida cohort. Neonates with the W allele displayed lower BMI (P < 0.001), ponderal index (P < 0.001), birth weight (P < 0.01), insulin levels (P < 0.05), the insulin/cortisol ratio (P < 0.05), HOMA-R (P < 0.05) and Apo B values (P < 0.01), but higher oxidised LDL (LDLox) values and a higher LDLox/low-density lipoprotein (LDL) ratio (both P < 0.05) than S-homozygous newborns. The APOA5 S19W polymorphism was associated with foetal growth as well as with glucose and lipoprotein metabolism in the neonates. Concurrence of the S19W polymorphism in neonates and their mothers did not affect neonatal lipid and lipoprotein concentrations but was associated with impaired foetal growth. Specifically, W allele carriers displayed a higher degree of LDL oxidation and lower body weight, plasma insulin values, insulin/cortisol ratio and Apo B concentrations than homozygotes for the common S allele. In conclusion, these findings suggest that the W allele carriers received a less optimal nutrition during gestation and that their lipoprotein antioxidant status was inferior to that of their homozygous S allele counterparts.     

Oxidative stress and increased type-IV collagenase levels in bronchoalveolar lavage fluid from newborn babies.

Oxidative stress may increase lung permeability by up-regulation of matrix-metalloproteinase-9 (MMP-9), a type-IV collagenase that can disrupt alveolar basement membranes. We have compared a marker of oxidative stress (protein carbonyl residues) with levels of MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in bronchoalveolar lavage samples from newborn babies. Bronchoalveolar lavage samples (n = 87, two from each time point) were taken in the first 6 postnatal days from 41 ventilated babies: 18 of <29 wk gestation, 10 of 29-36 wk, 9 term with persistent fetal circulation, and 4 term without lung disease. Respiratory disease severity at the time of bronchoalveolar lavage was assessed using the arterial-alveolar oxygen tension ratio. One sample from each time point was used for the measurement of MMP-9 by zymography and TIMP-1 by ELISA. The second sample was used to measure carbonyl group concentrations, also using an ELISA. Correlations were calculated between protein carbonyls, arterial-alveolar oxygen tension ratio, and MMP-9 and TIMP-1 concentrations. Significant correlations were found between carbonyl concentrations and arterial-alveolar oxygen tension ratio (r = -0.325, p = 0.0031, n = 81), MMP-9 (r = 0.331, p < 0.0029, n = 79), and TIMP-1 (r = 0.436, p < 0.0001, n = 87). Worsening respiratory disease in newborn babies is associated with increased carbonyl concentrations in neonatal bronchoalveolar lavage fluid, and these correlated with MMP-9 and TIMP-1 levels. Increased oxidative stress may damage the lung by increasing type-IV collagenase activity, causing disruption of the extracellular matrix.     

Vitamin E absorption in small premature infants.

The absorption of vitamin E, given by orogastric tube, was studied in premature infants who weighed less than 1.5 kg at birth. After the administration of either dl-alpha tocopherol or the acetate form, plasma tocopherol levels increased. In a second blind trial, 28 infants received either 25 units of dl-alpha tocopherol or placebo during the first six weeks of life. Plasma tocopherol levels in all treated infants were sustained in the normal adult range. The vitamin E-deficient state of premature infants can be corrected by oral therapy alone.     

Separation and characterization of cord serum lipoproteins.

Blood was collected from the umbilical cord of infants with a 1-min Apgar score of 9 to 10. Total cord serum lipoproteins were isolated by ultracentrifugation, at a density of 1.220 g/ml. The isolated serum lopoproteins were then separated by gel filtration chromatography on 6% agarose. The overall recovery of the separated lipoprotein cholesterol was 90% or greater. In cord serum, four lipoprotein peaks were found, whereas three peaks were present in adult lipoproteins. The major lipoproteins of cord serum correspond to low density lipoprotein (LDL) and high density lipoprotein (HDL). Very low density lipoproteins (VLDL) were heterogeneous in cord serum. After gel filtration chromatography, the distribution of cord serum cholesterol is about 5% in peak 1, 10% in peak 2, 40% in peak 3 (LDL), and 45% in peak 4 (HDL). An additional difference between the lipoproteins isolated from cord serum and those from adult serum was the slower electrophoretic mobility of cord serum VLDL in agarose gel.     

Lipoprotein alterations and plasma lipoprotein lipase reduction in familial hemophagocytic lymphohistiocytosis.

Serum lipid abnormalities are common in familial hemophagocytic lymphohistocytosis (FHL), a disorder also characterized by fever, hepatosplenomegaly, pancytopenia and a prominent lymphohistiocytic accumulation in the mononuclear phagocyte system. The lipoprotein pattern in nine children with FHL was studied with a quantitative method measuring cholesterol and triglycerides in each major class of lipoproteins. Triglycerides were markedly elevated during active FHL in serum, very low density lipoproteins, and low density lipoproteins. Cholesterol was increased in very low density lipoproteins whereas both triglycerides and cholesterol were extremely low in high density lipoproteins. These lipoprotein abnormalities, reversible on successful therapy, are compatible with a depressed lipolytic activity. Post-heparin levels of lipoprotein lipase and hepatic lipase in plasma were studied in four children and found to be markedly low during active FHL. We suggest that inflammatory cytokines, which may strongly suppress lipoprotein lipase activity, can be important mediators in the pathophysiology of FHL and that they may participate in the development of the lipid abnormalities.     

Lipoprotein Alterations and Plasma Lipoprotein Lipase Reduction in Familial Hemophagocytic Lymphohistiocytosis

ABSTRACT. Serum lipid abnormalities are common in familial hemophagocytic lymphohistocytosis (FHL), a disorder also characterized by fever, hepatosplenomegaly, pancytopenia and a prominent lymphohistiocytic accumulation in the mononuclear phagocyte system. The lipoprotein pattern in nine children with FHL was studied with a quantitative method measuring cholesterol and triglycerides in each major class of lipoproteins. Triglycerides were markedly elevated during active FHL in serum, very low density lipoproteins, and low density lipoproteins. Cholesterol was increased in very low density lipoproteins whereas both triglycerides and cholesterol were extremely low in high density lipoproteins. These lipoprotein abnormalities, reversible on successful therapy, are compatible with a depressed lipolytic activity. Post-heparin levels of lipoprotein lipase and hepatic lipase in plasma were studied in four children and found to be markedly low during active FHL. We suggest that inflammatory cytokines, which may strongly suppress lipoprotein lipase activity, can be important mediators in the pathophysiology of FHL and that they may participate in the development of the lipid abnormalities.     

Characterization of lipoprotein lipase activity in the newborn rat liver

Acetone ether powders of livers from starved newborn rats were applied to heparin-Sepharose affinity columns. The so-called hepatic triacylglycerol lipase was eluted with 0.9 M NaCl and a second lipolytic activity peak was eluted with 1.5 M NaCl. The behaviour of this 1.5 M NaCl-eluted fraction against increasing concentrations of serum, NaCl, protamine sulfate and heparin in the assay mixture was almost identical to that shown by partially purified lipoprotein lipase from adult rat adipose tissue, and clearly different from that shown by partially purified hepatic triacylglycerol lipase from the adult rat liver. We conclude that the newborn rat liver contains a lipoprotein lipase activity with similar properties to those found in adult adipose tissue lipoprotein lipase activity. It is suggested that this enzyme enables the neonatal liver to take up circulating triacylglycerols directly.     

Development aspects of renal beta-amino acid transport II. Ontogeny of uptake and efflux processes and effect of anoxia.

Renal cortex slices from newborn, 2-week, and 4-week-old Sprague-Dawley rats had reduced initial rates of taurine uptake compared to adult slices after short (less than 30 min) incubation periods. From birth onward, steady-state accumulation occurred by at least two sodium-dependent uptake systems. The first system had an "apparent Km1" = 0.1 mM and a Vmax varying from 1.8 to 5.1 mumoles/ml ICF/120 min at four ages. The second uptake mode had an apparent Km2 = 12-16 mM and a Vmax of 45 mumoles/ml ICF/120 min. Efflux of taurine was reduced in slices from younger animals possibly accounting for taurinuria. Only other beta-amino acids inhibited accumulation. Anoxia inhibited uptake at high concentration ( greater than 1.0 mM) at each age, but taurine accumulation at low concentrations ( less than 0.4 mM) was relatively protected from anoxia in neonatal ( less than 36 hr of age) tissue. Preincubation in taurine-free medium for 120 min enhanced low concentration, but not high concentration uptake in neonatal and 2-week slices. After preincubation in dibutyryl cyclic AMP (dbcAMP) enhanced uptake of taurine was found in adult cortex, but not in neonatal cortex. The ontogeny of renal taurine transport in cortex slices appeared to involve faster initial uptake rates and faster efflux as well as greater dependence on aerobic metabolism with maturation. Age-related differences in the response to preincubation and cyclic nucleotides were also indicative of maturation events in renal tubular amino acid transport.     

Low-density lipoprotein oxidizability in children with chronic renal failure

Background: In childhood, dyslipidemia and low-density lipoprotein (LDL) oxidation play an important role in the development of atherosclerosis. Alterations of these factors have been shown in adult uremic patients.
Methods: Nine children affected by chronic renal failure (CRF; urinary tract malformation, n = 8; polycystic kidney disease, n = 1) were studied to investigate the abnormalities of plasma lipoprotein concentration and composition and to assess the susceptibility of LDL to oxidation. All patients with CRF were on conservative treatment and, after informed consent, underwent the evaluation of (i) quantitative and qualitative plasma lipid profile; (ii) lipoprotein oxidation in vitro; and (iii) lipoprotein anti-oxidant content. These results were compared to those of an age-matched control group of eight healthy children.
Results: Total cholesterol, LDL and triglycerides were significantly higher in CRF than in the control group. The composition of lipoproteins was different in the two groups: the amount of anti-oxidant factors (α-, γ-tocopherol and carotenoids) was different in CRF and normal controls children, while LDL susceptibility to oxidation was significantly higher in uremic children than in controls.
Conclusions: CRF patients, already before dialysis, have a higher LDL oxidizability due to an altered lipoprotein composition and a low anti-oxidant content; therefore they have higher risk factors for atherosclerosis. On the basis of these data, supplementation with anti-oxidants might be useful in CRF children, but further studies are needed to evaluate the efficacy and safety of this therapeutic intervention.     

Serum lipoproteins in venous blood serum from birth to the end of the first week: feeding influences

Serum lipoproteins were explored on the first day of life (D1) and on the sixth day (D6) in blood drawn by peripheral venipuncture from 43 normal term newborns, 22 breast-fed and 21 formula-fed, and were compared to those of a control group of 28 young adults. With the exception of apolipoprotein E (Apo E), values of lipoprotein components obtained at D1 were similar, although generally slightly lower than those previously reported for cord blood serum. Total Apo E concentration at D1 (71 +/- 25 mg/l) was much higher than that obtained for the adult group (30 +/- 7 mg/l). Apo E distribution within the lipoprotein spectrum confirmed the presence of an already known Apo E-rich high density lipoprotein subfraction, which was responsible for the high total Apo E level at birth. The rise of lipoproteins of low density from D1 to D6, as evidenced by the increase of very low density lipoprotein + low density lipoprotein cholesterol and low density lipoprotein apolipoprotein B concentrations, was shown to be diet dependent. It was significantly less important in newborns fed a standard formula moderately enriched in unsaturated fatty acids than in breast-fed newborns.     

Lipoprotein alterations in children with bacterial meningitis

Abnormalities in serum lipids, including hypertriglycerideinia, are common during infectious disorders. However, the lipoprotein pattern during infections, particularly in children, has been investigated to only a limited extent. We have monitored alterations in serum lipoproteins in eight children with a severe baclcrial infcction (meningitis) by a quantitating method measuring cholesterol and triglyccrides in each major class. The levels of triglyccrides in serum and in low-density lipoproteins were markedly elevated during the infection, whereas the amount of cholesterol in high-density lipoprotcins was decreased. The cholesterol to triglyceride ratio was decreased in low-, as well as in high-density lipoproteins. These lipoprotein abnormalities may, at least in part, be explained by a depressed lipolytic activity of lipoprotein lipasc, the key enzyme for removal of triglycerides in man. Serum triglycerides and the levels of cholesterol in high-density lipoproteins, as well as the ratio between these parameters, may be used as indicators of inflammatory activity.     

Lipoprotein alterations in children with bacterial meningitis

Abnormalities in serum lipids, including hypertriglycerideinia, are common during infectious disorders. However, the lipoprotein pattern during infections, particularly in children, has been investigated to only a limited extent. We have monitored alterations in serum lipoproteins in eight children with a severe baclcrial infcction (meningitis) by a quantitating method measuring cholesterol and triglyccrides in each major class. The levels of triglyccrides in serum and in low-density lipoproteins were markedly elevated during the infection, whereas the amount of cholesterol in high-density lipoprotcins was decreased. The cholesterol to triglyceride ratio was decreased in low-, as well as in high-density lipoproteins. These lipoprotein abnormalities may, at least in part, be explained by a depressed lipolytic activity of lipoprotein lipasc, the key enzyme for removal of triglycerides in man. Serum triglycerides and the levels of cholesterol in high-density lipoproteins, as well as the ratio between these parameters, may be used as indicators of inflammatory activity.     

Lipoprotein changes in small-for-gestational-age infants fed nucleotide-supplemented milk formula

Morillas J, Moltó L, Robles R, Gil A, Sánchez-Pozo A. Lipoprotein changes in small-for-gestational-age infants fed nucleotide-supplemented milk formula. Acta Prediatr 1994;83:481–5. Stockholm. ISSN 0803–5253
We determined the effect of supplementing milk formula with nucleotides on plasma lipoproteins in small-for-gestational-age infants: 21 infants were fed a nucleotide-supplemented formula and 20 infants were fed the same nucleotide-free formula. On days 0, 3 and 7 after birth, major plasma lipoprotein fractions were analyzed for apolipoprotein and lipid composition. Compared with the control group, the group receiving nucleotides had increased total apoprotein concentrations in all lipoproteins as well as increased apo A-I in high-density lipoproteins and very low-density lipoproteins, and apo B-100 in very low-density lipoproteins and low-density lipoproteins. Very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol and very low-density lipoprotein triglycerides increased in parallel to the changes in apoproteins. The cholesterol ester to unesterified cholesterol ratio was increased in low-density lipoproteins and, particularly, in high-density lipoproteins. These data support the hypothesis that lipoprotein metabolism in small-for-gestational-age infants is affected by dietary nucleotide supplementation, enhancing lipoprotein synthesis or secretion. Cholesterol esterification capacity paralleled the apo A-I increase, in agreement with the co-factor role of apo A-I on lecithin: cholesterol acyltransferase.