Serum fatty acid and lipoprotein subclass concentrations and their associations in prepubertal healthy Norwegian children

Introduction

The lipid metabolism is one of the most important and complex processes in the body. Serum concentrations of 18 fatty acids (FAs) and 24 lipoprotein features, i.e. concentrations of lipoprotein main and subclasses and average particle size in main classes, in 195 ethnic Norwegian children from the rural Fjord region were quantified by chromatography.

Objectives

To assess gender differences in prepubertal children and reveal predictive FA patterns for lipoprotein features.

Methods

Lipoprotein features were modelled from FA profiles using multivariate regression.

Results

Contrary to observations for adults from the same region, gender differences in prepubertal children were generally small. However, higher concentrations of C16–C18 FAs for girls compared to boys correlated to higher concentrations of triglycerides (TG) and very low density lipoprotein (VLDL) particles and larger average size of VLDL particles. Concentrations of high density lipoprotein (HDL) and its subclass of medium particle size were higher in boys than in girls. These findings are opposite to observations in adults from the same region, but reflect that prepubertal boys are more physically active than girls. Furthermore, children possessed only half the serum levels of eicosapentaenoic acid and docosahexaenoic acid measured in adults. Since sampling was done after 12 h of fasting, these differences may reflect higher rate of utilization of these crucial FAs in children.

Conclusion

Good predictive models were obtained for TGs, VLDL and chylomicrons with C14–C18 FAs as major contributors. Weak predictive associations were observed for HDL and Apolipoprotein A1 (ApoA1) with C20–C24 FAs as contributors.

     

Changes in serum sex hormone-binding globulin and in serum non-sex hormone-binding globulin-bound testosterone during prepuberty in boys

Much evidence suggests that sex hormone-binding globulin (SHBG) influences the delivery of sex steroids to cells, probably by playing an important role in the distribution of serum sex hormones between SHBG-bound, albumin (HSA)-bound and free fractions. Recent evidence also suggests that HSA-bound testosterone (T), the major constituent of non-sex hormone-binding globulin-bound T, is biologically important. To examine the potential exposure of peripheral tissues to T during prepubertal years, the serum concentration of SHBG as well as the distribution of serum T in SHBG-bound, HSA-bound, free and non-SHBG-bound fractions was studied in 80 normal boys aged 0.5-14 yr, all at Tanner's stage G1 of sexual development. A gradual decrease in serum SHBG as a function of age was found without significant changes in the Ka of SHBG-dihydrotestosterone association. While regression analysis of serum total T vs age showed a 2.6-fold increase from 0.5 to 14 yr of age, those of non-SHBG-found, HSA-bound and free T vs age showed 8- to 9-fold increases during the same period. On the other hand, SHBG-bound T had only a 1.9-fold increase. Expressed as a function of serum total T, non-SHBG-bound T increased from 6.6 to 30.4%, the relative increment being greater for HSA-bound T than for free T. It is concluded that, with advancing age, there is a progressive increase in the T exposure of all tissues in normal prepubertal boys. It is speculated that, at the level of the central nervous system, this increase in serum bioavailable T could induce maturative changes in brain cells that result in the onset of puberty in normal boys.     

Elevated serum free fatty acid concentrations inhibit T lymphocyte signaling.

Unbound cis-unsaturated free (i.e., nonesterified) fatty acids (FFA) inhibit T lymphocyte activation in vitro and therefore may exert immunosuppressive effects. However, in blood serum the major proportion of FFA is tightly bound to albumin, whereas unbound FFA are hardly detectable. Since serum FFA elevation occurs under pathological conditions like insulin resistance or cancer, which are often associated with a disturbed immune response, we addressed the question of whether increased serum FFA concentrations could affect T lymphocyte activation under in vivo conditions. Our studies revealed that 1) addition of pure long-chain cis-unsaturated FFA in the absence of albumin inhibited calcium response in cultured Jurkat T cells. 2) In healthy volunteers, serum FFA elevation by a lipid/heparin infusion, including predominantly unsaturated fatty acids, decreased calcium response of cultured T cells in contrast to studies without heparin. 3) Most notably, stepwise increasing serum FFA by lipid/heparin infusion also inhibited calcium response of simultaneously isolated autologous peripheral blood T lymphocytes as well as their CD4(+) and CD8(+) subsets. In conclusion, our data emphasize that serum FFA elevation is able to exert immunosuppressive effects in vivo.     

Omega-3 fatty acid deficiency during brain maturation reduces neuronal and behavioral plasticity in adulthood

Omega-3-fatty acid DHA is a structural component of brain plasma membranes, thereby crucial for neuronal signaling; however, the brain is inefficient at synthesizing DHA. We have asked how levels of dietary n-3 fatty acids during brain growth would affect brain function and plasticity during adult life. Pregnant rats and their male offspring were fed an n-3 adequate diet or n-3 deficient diets for 15 weeks. Results showed that the n-3 deficiency increased parameters of anxiety-like behavior using open field and elevated plus maze tests in the male offspring. Behavioral changes were accompanied by a level reduction in the anxiolytic-related neuropeptide Y-1 receptor, and an increase in the anxiogenic-related glucocorticoid receptor in the cognitive related frontal cortex, hypothalamus and hippocampus. The n-3 deficiency reduced brain levels of docosahexaenoic acid (DHA) and increased the ratio n-6/n-3 assessed by gas chromatography. The n-3 deficiency reduced the levels of BDNF and signaling through the BDNF receptor TrkB, in proportion to brain DHA levels, and reduced the activation of the BDNF-related signaling molecule CREB in selected brain regions. The n-3 deficiency also disrupted the insulin signaling pathways as evidenced by changes in insulin receptor (IR) and insulin receptor substrate (IRS). DHA deficiency during brain maturation reduces plasticity and compromises brain function in adulthood. Adequate levels of dietary DHA seem crucial for building long-term neuronal resilience for optimal brain performance and aiding in the battle against neurological disorders.     

Changes in fatty acid compositions of mitochondria during embryonic development

1. A general trend among biomembranes of hepatocytes in the developing avian embryo is to display increasing percentages of unsaturated fatty acids, especially oleic acid (C18:1). 2. However, once increasing amounts of thyroxine appear in the plasma, mitochondria begin to exhibit increasing percentages of saturated fatty acids, primarily stearic acid (C18:0). 3. Increasing saturation of mitochondrial membrane lipids can be inhibited by exposure of embryonated eggs to 500 R of X-irradiation. 4. Injection of embryonated eggs with estrone increases the proportion of oleic acid (C18:1) in mitochondrial membranes but a balancing increase in palmitic acid (C16:0) enables their lipids to remain more saturated than unsaturated.     

Interrelationships between low density lipoprotein receptor defect, serum fatty acid composition, and serum cholesterol concentration

It is known that, in the general human population, serum fatty acid composition is correlated with serum triacylglycerol and cholesterol concentrations. The goal of the present study was to analyze whether the same is true of individuals who have a low density lipoprotein receptor (LDL-R) defect. Concentrations of 16 different fatty acids, cholesterol, triacylglycerol, and major lipoproteins in serum were determined in eight individuals who had (FH-North Karelia), the most common LDL-R defect in Finland, which causes familial hypercholesterolemia, and in their 30 relatives belonging to a single large pedigree as controls. The average number of double bonds (i.e., degree of desaturation) in serum fatty acids correlated negatively with the concentrations of serum total cholesterol (r = 0.27, P < 0.05) and total triacylglycerol (r = -0.71, P < 0.001) and positively with the number of fish meals per week (r = 0.50, P < 0.01), which was analyzed in all pedigree members jointly. These effects were similar in individuals having LDL-R defect, in which group the correlation coefficients were -0.31 (P = NS), -0.99 (P < 0.001), and 0.79 (P = NS) for serum total cholesterol, triacylglycerol, and weekly fish meals, respectively. Thus, LDL-R defect does not impair the correlation between serum fatty acid composition and serum triacylglycerol concentration. This result is in agreement with dietary studies that have shown that familial hypercholesterolemia patients respond very favorably to dietary therapy.     

Changes of serum albumin affinity for aspirin induced by fatty acid

Saturated fatty acids such as myristic acid play an important role in the pathogenesis of cardiovascular disorders.

Using the quenching fluorescence method we examined the influence of myristate on the changes of transporting protein affinity towards aspirin—the most popular anticoagulant.

Our results showed that the presence of the myristic acid alters the stability of the anticoagulant–albumin complex. The ranges of [myristate]/[albumin] molar ratio at which the stability of drug–protein complex increases or decreases were determined. The differences in interaction between ligands and human or bovine serum albumins were identified. The competition in binding of ligands with these albumins was also described.     

Changes in LH pulse frequency and serum progesterone concentrations during the transition to breeding season in ewes

To characterize the changes in LH pulse frequency during the transition to breeding season. LH pulse patterns and serum progesterone profiles were determined in 8 intact ewes from mid-anoestrus to the early breeding season. Overall, 8 increases in LH pulse frequency were observed and these were restricted to 5 ewes. Of the 8 increases, 7 occurred during the 4 weeks before the first cycle, 5 of them within 1 week after a pulse frequency typical of anoestrus (0-2 per 8 h). Six of them occurred less than 1 week before either a full-length luteal phase (n = 2) or a 1-3-day increment in progesterone (n = 4). Seven of these brief progesterone increases were observed in 6 ewes, 5 of them immediately preceding the first full-length luteal phase. These results are consistent with the hypothesis that the seasonal decrease in response to oestradiol negative feedback at the beginning of the breeding season causes an increase in GnRH, and thereby LH pulse frequency. In addition, they demonstrate that the first increase in tonic LH secretion occurs in less than 1 week and, in most ewes, initiates either the first full-length cycle or a transient increase in progesterone, the latter occurring more often.     

Serum amino acid concentrations in aging men and women

The age and gender related differences in serum amino acid concentrations have been assessed in 72 (23-92 years) medically screened healthy men and women who were divided into three male and three female groups according to age. Free-time physical activity and food intake were analysed from the 5-day diaries. The subjects were instructed to eat according to their normal dietary habits and to avoid any clinical complementary nutritional products or other products that could increase protein or energy intake. The blood samples (5 ml) taken from the antecubital vein after an over-night fast were analysed for their amino acid contents by chromatography. In total nutrient intake of energy (P < 0.001), protein (P < 0.001), alcohol (P < 0.05), water (P < 0.01), sodium (P < 0.001) and fiber P < 0.001) decreased significantly with age. The concentration of total amino acids (P < 0.01), essential amino acids (P < 0.001), non-essential amino acids (P < 0.05) and branched-chain amino acids (P < 0.05) decreased, whereas citrulline (P < 0.001) and cysteine (P < 0.001) were the only amino acids, which increased with aging. In addition, men had significantly higher concentrations than women of essential amino acids (P < 0.001), branched-chain amino acids (P < 0.001), and 10 of the 22 individual amino acids assayed (P < 0.01). Women had significantly higher concentrations of aspartate (P < 0.05), glycine (P < 0.01), serine (P < 0.001) and taurine (P < 0.01) than men. It is concluded that the decrease in serum total amino acid concentration is associated with decreased energy and protein intake with aging and men have higher essential amino acid concentration in serum than women.     

Changes in free amino acid concentrations in serum,brain, and CSF throughout embryogenesis

Using the developing chick embryo as a model and a very sensitive micromethod for amino acid analysis, a complete analysis is presented of the developmental changes in free amino acid concentration in the blood, in the CSF, and in two different brain regions (optic lobe and frontal lobe) of the chick embryo (from day 4 of incubation, until day 5 post hatching). The developmental profile of Lys is the only one that is almost identical in all three compartments. The developmental profiles of the serum and of the brain are very similar for Arg and Phe, less so for Leu and Gly, and towards the end of the embryonic period, similar also for Val, Ile, Trp, and Met. The amino acid concentrations in the CSF are either much lower than in serum and brain already at the earliest stages, or they progressively decline to levels lower than those in brain and serum, most rapidly between day 6 and 8 of embryonic life. The concentrations of neuroactive amino acids (Gln, Glu, Asp, GABA, Tau, and Gly) in both brain regions begin to increase very early, and continue to rise, except Tau, which goes through a maximum at day 8. Comparative analysis of the developmental profiles of each amino acid in serum, brain, and CSF reveals that the blood supply and the cellular uptake, retention, and metabolism by neural cells are the major determinants of the free amino acid pool of the developing brain.     

Changes in DNA repair during aging

DNA is a precious molecule. It encodes vital information about cellular content and function. There are only two copies of each chromosome in the cell, and once the sequence is lost no replacement is possible. The irreplaceable nature of the DNA sets it apart from other cellular molecules, and makes it a critical target for age-related deterioration. To prevent DNA damage cells have evolved elaborate DNA repair machinery. Paradoxically, DNA repair can itself be subject to age-related changes and deterioration. In this review we will discuss the changes in efficiency of mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER) and double-strand break (DSB) repair systems during aging, and potential changes in DSB repair pathway usage that occur with age. Mutations in DNA repair genes and premature aging phenotypes they cause have been reviewed extensively elsewhere, therefore the focus of this review is on the comparison of DNA repair mechanisms in young versus old.     

Changes in glycerolipids and their fatty acid composition during maturation of tobacco seeds

Triacylglycerol, which was one of the minor lipid components in immature seeds of tobacco, accumulated dramatically between 7 and 27 days after flowering and, in mature seeds at 37 days, the fatty acid methyl esters of the triacylglycerols comprised 96.3% of those of the total lipids. Diacylglycerols and sterol ester also increased significantly during seed development. Phosphatidylcholine and phosphatidylethanolamine, which were major components in immature seeds, decreased constantly with increasing maturation as well as the quantities of phosphatidylinositol and phosphatidylglycerol. Monogalactosyldiacylglycerols, digalactosyldiacylglycerols and sulfoquinovosyldiacylglycerols also decreased and disappeared in mature seeds. In the triacylglycerols the percentages of palmitate, stearate and linolenate fell with increasing seed age, while that of linoleate increased up to 75.3% in mature seeds. A similar trend was observed in the fatty acid composition in the diacylglycerols and sterol ester. Generally, in the phospholipids the proportions of linoleate and linolenate decreased with concomitant increases of stearate and oleate.     

Changes in fatty acid composition of sulfolipid and phospholipids during maturation of alfalfa

Lipids were extracted from alfalfa samples collected at intervals over the growing season and were fractionated to yield pure sulfolipid. In the sulfolipid and in a phospholipid fraction the major fatty acids were palmitic, linolenic, and linoleic, of which the palmitic acid increased in proportion during the season while the proportion of linolenic acid dropped. The sulfolipid contained more linolenic acid and less palmitic and linoleic acids than the phospholipids, and had a greater rate of change of fatty acid composition.     

Zinc and copper concentrations in serum from Spanish women during pregnancy

A cross-sectional study of serum zinc (Zn) and copper (Cu) levels in 31 healthy pregnant women and 51 healthy, nonpregnant controls living in the Mediterranean area of Granada, Spain, was performed. The subjects were divided into two groups: Group A, consisted of pregnant women in three categories according to the trimester of pregnancy, and Group B consisted of nonpregnant women acting as controls. In pregnant women, serum Zn levels were found from 0.300-1.340 mg/L and serum Cu from 0.936-2.304 mg/L, whereas in the nonpregnant women group, the mean serum levels were 0.947 ±0.265 mg/L for Zn and 1.092 ±0.365 mg/L for Cu. Serum Zn progressively decreased with gestation. Mean Zn levels were 0.829 ±0.253, 0.846 ±0.329, and 0.620 ±0.142 mg/L, corresponding to the first, second, and third trimesters of pregnancy, respectively. Serum Zn concentrations were significantly lower in pregnant women as compared to controls: 0.712 ±0.236 mg/L vs 0.947 ±0.265 mg/L, respectively (p < 0.05). In contrast, Cu levels increased with period of gestation from 1.053 ±0.498 mg/L in the first trimester to 1.616 ±0.304 mg/L in the second and 1.689 ±0.344 mg/L in the third. Serum Cu levels in the second and third trimesters of pregnancy were significantly higher (p < 0.05) than those determined during the first trimester and for nonpregnant controls. Both Zn and Cu during pregnancy did not appear to be dependent on the subject’s age (p > 0.05).     

The very low density lipoprotein receptor is not necessary for maintaining brain polyunsaturated fatty acid concentrations

Polyunsaturated fatty acids (PUFA), especially docosahexaenoic and arachidonic acids, as well as cholesterol are important for neural development and maintaining brain function. However, in contrast to cholesterol, the brain is unable to synthesize the required amounts of these PUFA de novo and requires a constant supply from plasma. Suggested pools of uptake include plasma unesterified PUFA or the uptake of PUFA-containing lipoproteins via lipoprotein receptors into endothelial cells of the blood brain barrier. Our study tested whether the very low density lipoprotein receptor (VLDLr) is necessary for maintaining brain PUFA and cholesterol concentrations. Moreover, since VLDLr knockout (VLDLr^?/?) mice have been reported to have behavioural deficits, this study asked the question whether altered brain PUFA and cholesterol concentrations might be related to these deficits. VLDLr^?/? and wild-type mice had ad libitum access to chow. At 7 weeks of age the mice were sacrificed, and the cortex, cerebellum, hippocampus, and the remainder of the brain were isolated for total fatty acid and cholesterol analyses. There were no differences in total lipid PUFA or cholesterol concentrations in any of the four brain regions between VLDLr^?/? and wild-type mice. These findings demonstrate that the VLDLr is not necessary for maintaining brain PUFA concentrations and suggest that other mechanisms to transport PUFA into the brain must exist.