Effect of metformin vs. placebo treatment on serum fatty acids in non-diabetic obese insulin resistant individuals.

Metformin improves insulin sensitivity, which is correlated to phospholipid fatty acid composition in obese type 2 diabetics. We aimed at investigating the relationship between Metformin and fatty acids in obese insulin resistant non-diabetic individuals. A double-blind, placebo-controlled 20-week trial was performed in 21 BMI and age-matched insulin resistant non-diabetic individuals receiving either Metformin or placebo. Insulin sensitivity together with metabolic parameters and fatty acids in serum phospholipids were measured at baseline and at 20 weeks. A significant decrease in body weight, BMI, percentage body fat, the sum of saturated fatty acids in serum phospholipids and increase in insulin sensitivity index were observed following the 20-week treatment. These changes did not differ significantly between the groups. Energy restriction rather than Metformin treatment appears to be responsible for the observed changes. The associations previously found in diabetics between insulin sensitivity and phospholipid fatty acids may not be mediated by Metformin.

Obese type 2 diabetics and obese patients have comparable plasma phospholipid fatty acid compositions deviating from that of healthy individuals.

There exist controversial reports regarding the differences in phospholipid fatty acids in type 2 diabetic and obese patients as compared to controls. The study was aimed at assessing the combined effect of type 2 diabetes and obesity on the fatty acid composition of plasma phospholipids. The experimental group consisted of 23 Belgian obese type 2 diabetics on Metformin. Two control groups were used: healthy lean and obese individuals in the same BMI range as the diabetics. Plasma phospholipids were isolated and their fatty acids and vinyl ether moieties were determined. Significance was set at P < 0.01. Plasma phospholipid fatty acids and plasmalogen-derived dimethyl acetals in diabetics deviated in many respects from these of lean controls but were not significantly different from those of obese non-diabetic patients. Therefore, the deviations of the fatty acid pattern of plasma phospholipids in type 2 diabetes may be attributed to obesity rather than to diabetes itself.

In humans, the seasonal variation in poly-unsaturated fatty acids is related to the seasonal variation in violent suicide and serotonergic markers of violent suicide.

BACKGROUND: Depression is accompanied by a depletion of n-3 poly-unsaturated fatty acids (PUFAs). There is also a negative correlation between suicide and fish-oil intake (rich in n-3 PUFAs) across different countries. Both depression and suicide show a seasonal variation and are related to disorders in the serotonergic system. AIMS: The present study was carried out to determine if there is a seasonal variation in the PUFA fractions in serum phospholipids and whether there are significant relationships between lowered n-3 PUFA status and the seasonal variation in the number of suicide deaths and serotonergic markers of suicide. METHODS: We took monthly blood samples during 1 calendar year from 23 healthy volunteers and analyzed the PUFA composition in serum phospholipids and related those data to the annual variation in the mean weekly number of suicides for Belgium and the Bmax [3H]-paroxetine binding to platelets in the same 23 subjects. RESULTS: Significant annual rhythms were detected in the long-chain PUFAs only, i.e. arachidonic acid (C20: 4n-6; AA), eicosapentaenoic acid (C20: 5n-3; EPA), and docosahexaenoic acid (C22: 6n-3; DHA). There was a significant correlation between the changes over the last 2 weeks in AA and EPA and the mean weekly number of violent, but not nonviolent, suicide deaths in Belgium. There was a significant correlation between the PUFAs, AA and DHA, and the Bmax [3H]-paroxetine binding to platelets. CONCLUSIONS: Our results show that there is a true seasonality in long-chain PUFAs, such as AA, EPA and DHA. The results suggest that the seasonality in PUFAs may be related to the incidence of violent suicide and the expression of the serotonin transporter complex.

Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression.

Several studies have shown that major depression is accompanied by alterations in serum fatty acid composition, e.g. reduced n-3 fatty acids and an increased 20:4n-6/20:5n-3 ratio in serum. Moreover, pregnancy leads to depletion of maternal serum 22:6n-3 and after delivery maternal serum 22:6n-3 steadily declines further. Therefore, the aim of the present study was to investigate whether the postpartum fatty acid profile of maternal serum phospholipids (PL) and cholesteryl esters (CE) differs in women who develop postpartum depression compared to controls. We compared the fatty acid composition shortly after delivery of 10 women who developed postpartum depression and 38 women who did not. After delivery, 22:6n-3 and the sum of the n-3 fatty acids in PL and CE was significantly lower in the group of mothers who developed a postpartum depression. The ratio of Sigman-6/Sigman-3 fatty acids in PL was, postpartum, significantly higher in the depressed group as compared to the controls. The abnormalities in fatty acid status previously observed in major depression are now also confirmed in postpartum depression. These results indicate that pregnant women who are at risk to develop postpartum depression may benefit from a prophylactic treatment with n-3 PUFAs, such as a combination of 20:5n-3 and 22:6n-3.

FA composition of cholesteryl esters and phospholipids in maternal plasma during pregnancy and at delivery and in cord plasma at birth.

The purpose of this study was to assess the FA composition of both cholesteryl esters (CE) and phospholipids (PL) in maternal plasma during pregnancy and at delivery and in umbilical plasma at birth. A longitudinal study of 32 normal pregnant women was carried out with three cutoff points during pregnancy (first, second, and third trimester) and at delivery. Few significant differences occurred in the FA profile of maternal CE: 18:1n-9 increased, 18:2n-6 dropped slightly, and 18:3n-3 decreased with progressing gestation. In maternal PL, long-chain highly unsaturated FA concentrations dropped and were replaced by saturated FA as gestation progressed. Additionally, changes in saturated FA in PL occurred: Shorter-chain 16:0 was higher whereas longer-chain 18:0 was lower at delivery compared to early pregnancy. The FA profile of umbilical venous plasma was strikingly different from that of maternal plasma at delivery. Cord plasma CE contained more saturated and monounsaturated FA than maternal CE. The polyunsaturates 18:2n-6 and 18:3n-3 are lower in umbilical CE than in maternal CE whereas 20:4n-6 and 22:6n-3 are twice as high in umbilical CE. Cord plasma PL have a higher content of long-chain highly unsaturated FA than maternal plasma PL at delivery. In contrast to maternal plasma PL, 16:0 was lower and longer-chain saturated FA were higher in cord plasma PL. The FA profile of umbilical plasma at birth shows preferential accumulation of 20:4n-6 and 22:6n-3, with low concentrations of 18:2n-6 and 18:3n-3 in CE and PL, indicating a preferential supply of the fetus with long-chain highly unsaturated FA needed for fetal development.

Fatty acid composition of phospholipids and cholesteryl esters in maternal serum in the early puerperium.

The fatty acid composition of serum phospholipids (PL) and cholesteryl esters (CE) in 26 healthy pregnant women at the end of term and 1 and 3 days after delivery was analysed in order to determine whether the maternal serum fatty acid composition changes in the early puerperium. The composition of the saturated fatty acids significantly changes in the PL fraction: 16:0 decreased and 18:0 increased. Both 20:4n-6 and 20:5 n-3 significantly increased after parturition in serum PL while 22:6n-3 remained constant at the three sampling time points. The sum of HUFA was slightly higher 3 days postpartum compared to the prepartum data. The essential fatty acid index significantly increased after delivery. In the CE fraction too differences occurred during puerperium: 18:2n-6 and 20:4n-6 increased and 18:1n-9 decreased after parturition. The sum of the n-3 fatty acids in CE remained unaltered. The EFA index significantly improved both in PL as in CE after delivery. In conclusion, the previously reported changes in the fatty acid composition of PL and CE during normal pregnancy diminish shortly after delivery. In fact, very soon after delivery the maternal fatty acid composition returns to more normal values.

Maternal and umbilical fatty acid status in relation to maternal diet.

The aim of this study was to describe the dietary fat intake during pregnancy and to study the relationship between the intake of polyunsaturated fatty acids (PUFAs) and the fatty acid composition of maternal and umbilical plasma phospholipids (PLs) and cholesterol esters (CEs) at delivery. In addition, the contribution of food groups to the intake of total fat and fatty acids in the diet was quantified.Maternal and umbilical blood samples were collected at delivery from 30 healthy pregnant women. The women completed a food frequency questionnaire during the first and third trimesters. The total fat intake during pregnancy is 85 (SD 24) g/day. The mean intake of saturated fatty acids (SFAs) is 33.4 g/day, of monounsaturated fatty acids (MUFAs) 28.6 g/day and of PUFA 15.2 g/day. Major sources of fat, MUFA and PUFA are fats, oils and sauces. Major sources of SFA are meat and poultry followed by cheese and eggs. Meat and poultry contribute the most to the intake of 20:4n-6 whereas fish is the major source of 20:5n-3 (EPA) and 22:6n-3 (docosahexaenoic acid (DHA)) in the diet. Linoleic acid, EPA and DHA (w%) in PL of maternal plasma are positively related to the intake of these fatty acids during pregnancy. No association is found between the maternal intake of the two parent essential fatty acids (18:2n-6 and 18:3n-3) and their fraction in umbilical PL or CE. EPA and the sum of n-6 fatty acids (w%) in umbilical plasma PL are positively correlated with the dietary intake of these fatty acids.

Fat absorption and metabolism in bile duct ligated rats.

BACKGROUND: Bile excretion is obstructed in children with extrahepatic bile duct atresia (EHBA) resulting in fat malabsorption and disturbed lipid metabolism. AIM: Investigate if the bile duct ligated rat exhibits similar deviations as patients with EHBA under different feeding conditions. METHODS: 6 bile duct ligated Wistar rats and 12 matched paired controls were randomised over 3 feeding groups. Rats were killed 16 or 30 days postsurgery. Faeces, blood and livers were collected. Fat absorption was evaluated, markers for cholestasis and the fatty acid composition of serum phospholipids (PL) and cholesterol esters (CE) were determined. Fatty acid desaturation activities in liver microsomes were measured. RESULTS: Cholestatic bile duct ligated rats have a lower fat absorption coefficient and a lower fraction of 18:2n-6 and 18:3n-3 in serum triglycerides than their controls. This demonstrates that bile duct ligated rats suffer from fat malabsorption. In contrast to the observations in serum triglycerides, 18:2n-6 and 18:3n-3 were not reduced in serum PL and CE of cholestatic rats. Overflow of 18:2n-6 rich biliary PL in the general circulation could contribute to this observation. In agreement with what was found in man, serum PL of cholestatic rats have a higher 16:0/18:0 ratio, increased monoenes and reduced unsaturated fatty acids. However, no differences were observed in microsomal desaturation activities. CONCLUSION: Cholestatic bile duct ligated rats exhibit similar deviations in serum fatty acid composition as found in patients with EHBA, therefore they can be used as a model for this human disease.

Oxidative stability of low density lipoproteins and vitamin E levels increase in maternal blood during normal pregnancy.

In 24 healthy pregnant women, parameters related to the oxidative stability of low density lipoproteins (LDL) were determined at three times during pregnancy and shortly after delivery. The fatty acid composition of plasma phospholipids (PL) and the plasma concentrations of vitamin E, vitamin A, and beta-carotene were assessed in the same samples. Total triglyceride (TG), total cholesterol, LDL-cholesterol, and high density lipoprotein (HDL)-cholesterol concentrations were also determined. The length of the lag phase of isolated LDL challenged with Cu2+ ions significantly increased with the progression of pregnancy. The oxidation rate and the amount of conjugated dienes formed increased and reached a maximum at 29-37 wk of pregnancy. Total TG, cholesterol, and LDL-cholesterol reached a maximum in the third trimester of pregnancy. beta-Carotene remained stable, vitamin A decreased, and vitamin E significantly increased throughout pregnancy. Vitamin E plasma concentration correlated positively with the length of the lag phase. The increased levels of vitamin E could contribute to the higher resistance of LDL toward oxidation with progressing gestation, measured by the prolonged lag phase. Furthermore, vitamin E plasma levels correlated positively with TG concentration but not with LDL-cholesterol. The level of polyunsaturated fatty acids in PL decreased with the progression of pregnancy. No correlation was found between the fatty acid composition of plasma PL, nor with the cholesterol concentration, and the parameters studied related to the oxidative stability of LDL. The major finding of this study is the increased oxidative resistance of LDL with progressing gestation.

The composition of saturated fatty acids in plasma phospholipids changes in a way to counteract changes in the mean melting point during pregnancy.

It has been demonstrated that in pathological conditions with an increase in the calculated mean melting point (MMP) of phospholipid (PL) fatty acids (FA) there are changes in the composition of the saturated FA (SFA), which partially counteract this effect: shorter-chain SFA with lower melting points are increased, while longer-chain less fluid SFA are suppressed. The aim of this study was to determine whether there are differences in MMP during pregnancy and in the newborn and, if so, whether similar adaptive changes occur in the composition of the SFA. The FA composition of plasma PL was determined in healthy women (n = 16) twice during pregnancy (15-24 wk and 29-36 wk) and at delivery and in umbilical venous blood obtained at birth. The MMP of maternal PL was significantly higher at delivery compared to mid-gestation, due to a loss of highly unsaturated FA (HUFA) which were replaced by SFA. In addition, changes in the SFA occurred: 16:0 with lower melting point was higher while 18:0 with higher melting point was lower at delivery. MMP of PL FA in umbilical plasma was lower than in maternal plasma at delivery, which was due to higher HUFA content. In contrast to maternal plasma, 16:0 was lower while 18:0, 20:0, and 24:0 were higher in umbilical plasma resulting in a higher MMP of SFA, tending to raise the overall MMP. It can be concluded that, during pregnancy and in the newborn, the FA composition of SFA changes in a way to counteract changes in MMP induced by reduced and increased HUFA, respectively.

Estimation of dietary fat intake of Belgian pregnant women. Comparison of two methods.

AIM: To evaluate the validity and usefulness of a food frequency questionnaire (FFQ) which was designed to evaluate individual fat consumption for a Dutch population relative to 7-day estimated records (7d ER). The FFQ has been validated previously and was adapted to the Belgian situation. METHODS: Longitudinal study in 26 healthy pregnant women; FFQ and 7d ER were obtained during the 1st and 3rd trimesters. RESULTS: FFQ was validated with 7d ER. Fat and fatty acid intake estimated by the FFQ did not differ significantly (p < 0.01) from data obtained by the 7d ER except for 18:2n-6. Pearson correlation coefficient between the 2 methods ranged from 0.62 to 0.68. On average, 47% of the women were classified in the same quartile with the 2 methods and less than 2% in the opposite quartile. Total fat intake, calculated from FFQ, was on average 87.9 (SD 18.1) g/day. The mean intake of linoleic acid was 13.3 (SD 5.4) g/day and of alpha-linolenic acid was 1.4 (SD 0.5) g/day. The dietary intake of the saturated, monounsaturated and polyunsaturated fatty acids was respectively 34.7 (SD 10.0) g/day, 29.6 (SD 8.1) g/day and 15.7 (SD 5.9) g/day. CONCLUSION: The FFQ gives similar results for fat intake as the 7d ER and is thus considered an appropriate method for classifying individuals to the right part of the distribution of dietary fat intake.

The effects of combined conventional treatment, oral antioxidants and essential fatty acids on sperm biology in subfertile men.

We evaluated the effects of combined conventional treatment, oral antioxidants (N-acetyl-cysteine or vitamins A plus E) and essential fatty acids (FA) on sperm biology in an open prospective study including 27 infertile men. The evaluation included sperm characteristics, seminal reactive oxygen species (ROS), FA of sperm membrane phospholipids, sperm oxidized DNA (8-OH-dG), and induced acrosome reaction (AR). Treatment did not improve sperm motility and morphology, nor decrease the concentration of round cells and white blood cells in semen. Sperm concentration increased in oligozoospermic men (7.4+/-1.3 to 12.5+/-1.9 million/ml). Treatment significantly reduced ROS (mean+/-SEM) (775.3+/-372.2 to 150.3+/-105.2 x 10(3)counts/10 second) and 8-OH-dG (45.3+/-10.4 to 16. 8+/-3.3 fmol/microg DNA). Treatment increased the AR (55.1+/-2.2 to 71.6+/-2.2%), the proportion of polyunsaturated FA of the phospholipids, and sperm membrane fluidity. The overall pregnancy rate was 4.5% in 134 months. The per month pregnancy rate tended to be higher in partners of (ex)-smokers (7.15%, n=14,70 months) than in never-smokers (1.6%, n=13,64 months) (OR:4.57, 95% Cl:0.55-38.1).

Substituting enzymatically interesterified butter for native butter has no effect on lipemia or lipoproteinemia in Man.

The aim of this study was to determine whether substituting enzymatically interesterified butter for native butter in the usual diet affects lipid and lipoprotein levels in man. Parameters studied were serum total cholesterol, LDL-cholesterol, HDL-cholesterol, free cholesterol, phospholipids, triglycerides, apoA1 and apoB and the fatty acid composition of serum triglycerides, free fatty acids, phospholipids and cholesterol esters. Subjects were healthy volunteers and a controlled design was used. The only mathematically significant difference found when interesterified butter was substituted for butter was an about 7% lower fraction of oleic acid in the serum cholesterol esters (p = 0.005). In contrast to an earlier study where chemically interesterified butter fat was substituted for native butter, no indications are found in this study that replacing native butter by enzymatically interesterified butter, in amounts normally consumed, may have any beneficial effect on health.

Mechanisms and effects of male genital tract infection on sperm quality and fertilizing potential: the andrologist's viewpoint.

There are several mechanisms acting in synergism that can impair sperm characteristics of patients with accessory gland infection. In some cases, conventional sperm variables are disturbed with oligo and/or asthenozoospermia. In other patients, these sperm variables may appear normal, but the functional capacity of spermatozoa may be impaired. In particular, changes in the composition of the sperm membrane may result in reduced acrosome reactivity and capacity to fuse with the oolemma, and oxidative damage of the sperm DNA may induce mutagenesis. Changes in the biochemical make-up of seminal plasma can also reduce the in-vivo fertilizing capacity of spermatozoa, and infection-related disruption of the blood-testis barrier can induce the generation of anti-sperm antibodies and immunological infertility. Many of these functional abnormalities will not become evident upon 'basic semen analysis', which explains why some authors are unable to link infection of the accessory sex glands to subfertility. Also, functional and anatomical damage acquired as a result of infection is often permanent and not reversible by (antibiotic) treatment. Clearly, there are many more aspects of male accessory gland infection that require investigation. Available data should stimulate clinicians to place more emphasis on the prevention of infection-related infertility than on its treatment, as the latter is often unsuccessful.

White blood cells cause oxidative damage to the fatty acid composition of phospholipids of human spermatozoa.

The lipid composition of the sperm membrane has been shown to exert a significant effect upon the functional quality of spermatozoa. We have studied the effect of induced peroxidation and of the presence of polymorphonuclear white blood cells (WBCs) on the fatty acid composition of the phospholipids of human spermatozoa. The spermatozoa were fractionated by a discontinuous Percoll gradient in two fractions (47% and 90% Percoll). Induced peroxidation of spermatozoa was assessed by determining the production of thiobarbituric acid reactive substances (TBARS), mostly malondialdehyde, after incubation with ferrous sulphate and sodium ascorbate as a promoter of peroxidation. TBARS production after induction of peroxidation was correlated with the abundance of polyunsaturated fatty acids (PUFA)(r = 0.68, p < 0.0001), with the double bond index (r = 0.72, p < 0.0001), and with the oxidative potential index (r = 0.73, p < 0.0001) of fatty acids of phospholipids. In comparison with samples containing > 1 x 10(6) WBCs/mL, those with < 1 x 10(6) WBCs/mL contained higher proportions of PUFA (90% Percoll, p < 0.05; 47% Percoll, p < 0.05), total omega 3 fatty acids (90% Percoll, p < 0.05; 47% Percoll, p < 0.001), docosahexaenoic acid (90% Percoll p < 0.05; 47% Percoll, p < 0.05), and double bond index (90% Percoll, p < 0.05; 47% Percoll, p < 0.001). In addition, mean melting point was significantly lower (90% Percoll, p < 0.05; 47% Percoll, p < 0.001) in samples with < 1 x 10(6) WBCs, indicating higher membrane fluidity. The increase of TBARS production by spermatozoa after incubation with the xanthine-xanthine oxidase system and/or ferrous sulphate as promoter of peroxidation was associated with a significant decrease of PUFA. Incubation of spermatozoa with WBCs, with or without activation by phorbol ester, decreased the PUFA (p < 0.05). Also, TBARS production was increased (p < 0.01) after activation of WBCs with phorbol ester. Our data provide evidence that oxidative stress induced by WBCs has a damaging effect on the polyunsaturated fatty acids of sperm phospholipids which may result, amongst other effects, in decreased membrane fluidity.

The fatty acid composition of phospholipids of spermatozoa from infertile patients.

The lipid composition of the sperm membrane has a significant effect upon the functional characteristics of spermatozoa. In the present study we investigated the fatty acid (FA) composition of subpopulations of spermatozoa separated on a discontinuous Percoll gradient (47:90%) and the FA composition of phospholipids (PL) of sperm heads and tails in both normal and abnormal semen samples. In normozoospermic samples, polyunsaturated fatty acids (PUFA) represented 34.0 +/- 1.3 (mean +/- SE, mole %) and 25.6 +/- 1.2% of total FA of PL of the 47 and 90% Percoll fractions respectively. Docosahexaenoic acid (22:6omega3, DHA) contributed to more than 60% of total PUFA. DHA was significantly lower in both the 47% (P < 0.05) and the 90% (P < 0.01) Percoll fractions of oligozoospermic samples and in the 90% Percoll layer of asthenozoospermic samples (P < 0.01), compared with normozoospermic samples. The omega6/omega3 ratio was significantly increased in both Percoll fractions of samples with oligozoospermia (47%, P < 0.001 and 90%, P < 0.001) or with asthenozoospermia (47%, P < 0.05 and 90%, P < 0.001) compared with normozoospermic samples. The oxidative potential index (OPI) of spermatozoa recovered from the 47% Percoll layer was significantly higher (P < 0.0001) than of those recovered from the 90% Percoll. Mean melting point (MMP), an index of membrane fluidity, was significantly lower in head than in tails (P < 0.01) of spermatozoa, and also in both the 47% (P < 0.01) and 90% (P < 0.001) Percoll fractions of normozoospermic samples in comparison with oligozoospermic samples. The MMP was significantly higher (P < 0.05) in samples of patients with idiopathic oligo/asthenozoospermia, varicocele, and male accessory gland infection (MAGI). These differences in FA composition of PL in subpopulations of human spermatozoa, and in their heads and tails may be related to sperm maturity and to differences in physiological function.

Serum fatty acid profiles in cystic fibrosis patients and their parents.

Fatty acid compositions of the major serum lipid classes from 43 cystic fibrosis (CF) homozygotes (CF patients), 36 obligate heterozygotes (parents of CF patients) and 34 controls were determined by capillary gas chromatography. Fatty acid compositions of the homozygote CF patients were skewed in the direction of relative essential fatty acid deficiency in comparison with the controls. Less pronounced, but similar deviations from normal, were observed in the heterozygotes. Homozygotes with normal fatty acid compositions and heterozygotes with considerably disturbed fatty acid profiles were found.