Fatty Acid Composition Of Cholesterol Esters Research Articles

Evaluation of the serum cholesterol ester fatty acid composition in the elderly with subclinical atherosclerosis

Objective To investigate serum levels of cholesterol ester fatty acids in elderly patients with subclinical atherosclerosis (AS), in order to provide supportive laboratory data for early prevention of AS. Methods A retrospective study was undertaken on 180 elderly volunteers (age ≥60 years) who had received regular health checkups at Beijing Hospital in 2013, including 92 subclinical AS patients (the subclinical AS group) with carotid intima-media thickness (cIMT) greater than 1 mm and 88 healthy subjects (the control group). Venous blood samples were taken. Liquid chromatography tandem mass spectrometry was used to determine eleven serum cholesterol ester fatty acids, and enzyme activities of desaturases and elongases were estimated from product-to-precursor ratios. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (ApoAI), ApoB, high sensitivity C-reactive protein (hsCRP) and other biochemical indicators were analyzed with automatic biochemistry analyzers and the results were analyzed with independent sample t-test, nonparametric test and logistic regression. Results Compared with the control group, age, TC, LDL-C, ApoB, serum CE16: 1 and Δ9-desaturase were higher, and serum CE22: 6 was lower in the subclinical AS group (P<0.05). After adjustment for confounding factors such as age, gender, body mass index, TC, TG, HDL-C, and LDL-C, the odds ratio of serum CE22: 6 was 0.29 (95%CI: 0.11-0.78, Wald χ2: 6.009, P<0.05), compared with the highest quartile and the lowest quartile. However, no significant difference was found in serum CE16: 1 and Δ9-desaturase. Spearman partial correlation analysis was used to analyze the relationship between CE22: 6 and the cardiovascular disease risk index and revealed that CE22: 6 was negatively correlated with Apo A, TC and HDL-C (r=-0.166, -0.149 and -0.194, respectively, each P<0.05), while no significant correlation with other indicators was found. Conclusions Serum CE22: 6 may play a protective role in subclinical AS patients. A balanced intake of fatty acids is helpful for prevention of AS in elderly people. Key words: Fatty acids; Docosahexaenoic acid ester; Atherosclerosis

High-oleic canola oil consumption enriches LDL particle cholesteryl oleate content and reduces LDL proteoglycan binding in humans

Oleic acid consumption is considered cardio-protective according to studies conducted examining effects of the Mediterranean diet. However, animal models have shown that oleic acid consumption increases LDL particle cholesteryl oleate content which is associated with increased LDL-proteoglycan binding and atherosclerosis. The objective was to examine effects of varying oleic, linoleic and docosahexaenoic acid consumption on human LDL-proteoglycan binding in a non-random subset of the Canola Oil Multi-center Intervention Trial (COMIT) participants. COMIT employed a randomized, double-blind, five-period, cross-over trial design. Three of the treatment oil diets: 1) a blend of corn/safflower oil (25:75); 2) high oleic canola oil; and 3) DHA-enriched high oleic canola oil were selected for analysis of LDL-proteoglycan binding in 50 participants exhibiting good compliance. LDL particles were isolated from frozen plasma by gel filtration chromatography and LDL cholesteryl esters quantified by mass-spectrometry. LDL-proteoglycan binding was assessed using surface plasmon resonance. LDL particle cholesterol ester fatty acid composition was sensitive to the treatment fatty acid compositions, with the main fatty acids in the treatments increasing in the LDL cholesterol esters. The corn/safflower oil and high-oleic canola oil diets lowered LDL-proteoglycan binding relative to their baseline values (p = 0.0005 and p = 0.0012, respectively). At endpoint, high-oleic canola oil feeding resulted in lower LDL-proteoglycan binding than corn/safflower oil (p = 0.0243) and DHA-enriched high oleic canola oil (p = 0.0249), although high-oleic canola oil had the lowest binding at baseline (p = 0.0344). Our findings suggest that high-oleic canola oil consumption in humans increases cholesteryl oleate percentage in LDL, but in a manner not associated with a rise in LDL-proteoglycan binding.

The Pro12Ala polymorphism of the PPAR-γ2 gene affects associations of fish intake and marine n−3 fatty acids with glucose metabolism

Data on associations between marine n-3 fatty acids and glucose metabolism are inconsistent. Therefore, we explored effects of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor (PPAR)-gamma2 gene on associations of fish intake and dietary and plasma eicosapentaenoic and docosahexaenoic acid with glucose metabolism. The design comprises of the cross-sectional analysis. The Pro12Ala variant in the PPAR-gamma2 (PPARG) gene was genotyped in 571 non-diabetic relatives of subjects with type II diabetes. The dietary intake was measured by a 3-day food record, and the plasma cholesterol ester fatty acid composition was analysed with gas chromatography. Associations of dietary and plasma variables with insulin resistance and fasting and 2-h glucose and free fatty acid concentrations were analysed with multiple linear regression analysis. In men, there was a significant interaction between PPARG polymorphism and plasma docosahexaenoic acid on fasting free fatty acid concentration (P=0.036), and genotype-stratified models showed an inverse association in Pro homozygotes only (P=0.028). In women, the proportion of plasma eicosapentaenoic acid was higher in Ala-allele carriers compared to Pro homozygotes (1.67 vs 1.44% respectively, P=0.006). A significant interaction between PPARG polymorphism and fish intake on 2-h glucose was found in women (P=0.021), and genotype-stratified models suggested an inverse association in Ala-allele carriers only (P=0.039). The findings suggest that PPARG polymorphism might affect the plasma proportion of eicosapentaenoic acid and modulate the associations of fish intake and marine n-3 fatty acids with glucose metabolism and fasting free fatty acids.

Higher plasma docosahexaenoic acid is associated with reduced progression of coronary atherosclerosis in women with CAD

Fish intake, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and in some cases alpha-linolenic acid (ALA) have been associated with reduced risk of cardiovascular events and death. The association between n-3 fatty acids in plasma lipids and the progression of coronary artery atherosclerosis was assessed among women with established coronary artery disease (CAD). A prospective cohort study involved postmenopausal women (n = 228) participating in the Estrogen Replacement and Atherosclerosis Trial. Quantitative coronary angiography was performed at baseline and after 3.2 +/- 0.6 (mean +/- SD) years. Women with plasma phospholipid (PL) DHA levels above the median, compared with below, exhibited less atherosclerosis progression, as expressed by decline in minimum coronary artery diameter (-0.04 +/- 0.02 and -0.10 +/- 0.02 mm, respectively; P = 0.007) or increase in percentage stenosis (1.34 +/- 0.76% and 3.75 +/- 0.74%, respectively; P = 0.006), and had fewer new lesions [2.0% (0.5-3.5%) of measured segments (95% confidence interval) and 4.2% (2.8-5.6%), respectively; P = 0.009] after adjustments for cardiovascular risk factors. Similar results were observed for DHA in the triglycerides (TGs). EPA and ALA in plasma lipids were not significantly associated with atherosclerosis progression. Consistent with higher reported fish intake, higher levels of plasma TG and PL DHA are associated with less progression of coronary atherosclerosis in postmenopausal women with CAD.

Plasma fatty acid composition and incidence of coronary heart disease in middle aged adults: The Atherosclerosis Risk in Communities (ARIC) Study

Background and Aim: To prospectively investigate the relation of plasma cholesterol ester (CE) and phospholipid (PL) fatty acid (FA) composition with incidence of coronary heart disease (CHD). Methods and Results: 3 591 white participants in the Minneapolis field center of the Atherosclerosis Risk in Communities Study, aged 45–64 years, were studied. Plasma FA composition of CEs and PLs was quantified using gasliquid chromatography and expressed as percentage of total FAs. Incident CHD was identified during 10.7 years of follow-up. In both CE and PL fractions, the proportions of stearic (18:0) acid, dihomo- γ-linolenic (20:3n6) acid and total saturated fatty acids (SFAs) were significantly higher while arachidonic (20:4n6) acid and total polyunsaturated fatty acids (PUFAs) were significantly lower among participants who developed incident CHD (n=282). After adjusting for age, gender, smoking, alcohol drinking, sports activity, and non-FA dietary factors, the incidence of CHD was significantly and positively associated with the proportion of dihomo- γ-linolenic acid but inversely associated with arachidonic acid. The multiply-adjusted rate ratios (RRs) of CHD incidence for the highest versus the lowest quintile were 1.31 in CE and 1.44 in PL for dihomo- γ-linolenic acid ( p for trend: 0.05 and 0.017, respectively), 0.59 in CE and 0.65 in PL for arachidonic acid ( p: 0.016 and 0.024, respectively). Also significantly and positively associated with incident CHD were PL stearic acid and CE linolenic (18:3n3) acid. Only a borderline significant positive association was observed for total SFAs in CE (multivariate RRs across quintiles: 1.00, 1.15, 1.40, 1.62, 1.32; p=0.07). Total PUFAs or monounsaturated FA were not independently associated with CHD. Conclusions: Our study found a weak positive association of SFAs with incident CHD. Our findings also confirm that FA metabolism in the body, such as the activity of Δ-5 desaturase, which converts dihomo- γ-linolenic acid to arachidonic acid, may affect the development of CHD.

Phospholipid composition of reconstituted high density lipoproteins influences their ability to inhibit endothelial cell adhesion molecule expression

The ability of different phosphatidylcholine (PC) species to inhibit cytokine-induced expression of vascular cell adhesion molecule 1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) was investigated. PC species containing palmitoyl- in the sn-1 position and palmitoyl- (DPPC), arachidonyl- (PAPC), linoleoyl- (PLPC) or oleoyl- (POPC) in the sn-2 position were compared. These PC species were studied as components of reconstituted high density lipoproteins (rHDL) (containing apolipoprotein A-I [apoA-I] as the sole protein) or as small unilamellar vesicles (SUVs). The rHDL containing PLPC and PAPC inhibited VCAM-1 expression in activated HUVECs by 95 and 70%, respectively, at an apoA-I concentration of 16 micrometer. At this concentration of apoA-I, POPC rHDL inhibited by only 16% and DPPC rHDL did not inhibit at all. These differences could not be explained by differential binding of the rHDL to HUVECs. The same hierarchy of inhibitory activity was observed when these PC species were presented to the cells as SUVs but only when the SUVs also contained an antioxidant. It was concluded that rHDL PC is responsible for their inhibitory activity and that this varies widely with different PC species.

Fatty acid composition of serum cholesterol esters as a reflector of low‐saturated‐fat, low‐cholesterol diet in young children: the STRIP project

STRIP (the Special Turku coronary Risk factor Intervention Project) is an ongoing intervention trial which aims at a permanent reduction in the intake of saturated fat and cholesterol starting in childhood. A total of 75 intervention and 63 control children was studied consecutively at the ages of 7 and 13 mo, and 2, 3 and 5 y to evaluate the influence of such intervention on serum cholesterol ester (CE) fatty acid composition, a widely used biomarker of fatty acid intake. Analysis of 4‐d food records showed that total intake of fat and of saturated fat increased with age in both groups of children but was constantly lower in intervention than in control children, e.g. at the age of 5 y the mean intakes of total fat and of saturated fatty acids were 31.1 E% and 33.9 E% and 12.1 E% and 14.6E% in intervention and control children, respectively (p = 0.009 and 0.0001, respectively). Serum CE fatty acid compositions did not differ between the 2 groups at any age; the mean proportion of CE linoleic acid was 52.4% and 52.0% in 5‐y‐old intervention and control children, respectively. Correlation analysis showed, however, that the percentage of linoleic acid and of polyunsaturated fatty acids in CE reflected well the respective dietary intakes (r= 0.36; p = 0.0001 for both coefficients).In conclusion, CE fatty acid composition did not differ between the intervention and control groups, whereas CE linoleic and total polyunsaturated fatty acids reflected well the differences in their intakes at the individual level.

Serum cholesterol ester fatty acids in 7‐ and 13‐month‐old children in a prospective randomized trial of a low‐saturated fat, low‐cholesterol diet: the STRIP baby project

To evaluate changes that occur in serum cholesterol ester fatty acid composition during the transition from typical infant feeding to a more adult type of nutrition, this study compared the effects on serum cholesterol ester fatty acids of breast milk or formula at the age of 7 mo with effects caused by 6‐mo dietary intervention in 137 children. The intervention [Special Turku coronary Risk factor Intervention Project for children (STRIP baby project)] aimed at a reduction of saturated fat intake to 10% of energy after the age of 1 y without purposefully influencing total fat intake. Nutrient intakes were calculated from 3‐d food records. At the age of 7 mo, i.e. before dietary education began, milk type markedly influenced dietary and serum cholesterol ester fatty acid composition (mean serum cholesterol ester 16:0 in breastfed vs formula‐fed infants, 13.7% vs 12.0%, respectively, p &lt; 0.001; serum cholesterol ester 18:2n‐6 50.6% vs 57.6%, p &lt; 0.001). At the age of 13 mo the calculated fat intake of the intervention and control children differed markedly but serum cholesterol ester fatty acid compositions in all children resembled closely those measured in 7‐mo‐old breastfed infants, e.g. at the age of 13 mo the relative proportions of 18:2n‐6 were 49.9% and 51.1% in previously formula‐fed intervention and control children, respectively, and 50.3% and 50.1% in previously breastfed intervention and control children, respectively. In conclusion, serum cholesterol ester fatty acid composition reflected differences in dietary fat quality (breast milk or formula) at the age of 7 mo, whereas dietary intervention as applied in the STRIP baby project had only a minimal effect. □Cholesterol esters, dietary intervention, fatty acids, infant feeding

Serum cholesterol ester fatty acids in 7- and 13-month-old children in a prospective randomized trial of a low-saturated fat, low-cholesterol diet: the STRIP baby project

To evaluate changes that occur in serum cholesterol ester fatty acid composition during the transition from typical infant feeding to a more adult type of nutrition, this study compared the effects on serum cholesterol ester fatty acids of breast milk or formula at the age of 7 mo with effects caused by 6-mo dietary intervention in 137 children. The intervention [Special Turku coronary Risk factor Intervention Project for children (STRIP baby project)] aimed at a reduction of saturated fat intake to 10% of energy after the age of 1 y without purposefully influencing total fat intake. Nutrient intakes were calculated from 3-d food records. At the age of 7 mo, i.e. before dietary education began, milk type markedly influenced dietary and serum cholesterol ester fatty acid composition (mean serum cholesterol ester 16:0 in breastfed vs formula-fed infants, 13.7% vs 12.0%, respectively, p < 0.001; serum cholesterol ester 18:2n-6 50.6% vs 57.6%, p < 0.001). At the age of 13 mo the calculated fat intake of the intervention and control children differed markedly but serum cholesterol ester fatty acid compositions in all children resembled closely those measured in 7-mo-old breastfed infants, e.g. at the age of 13 mo the relative proportions of 18:2n-6 were 49.9% and 51.1% in previously formula-fed intervention and control children, respectively, and 50.3% and 50.1% in previously breastfed intervention and control children, respectively. In conclusion, serum cholesterol ester fatty acid composition reflected differences in dietary fat quality (breast milk or formula) at the age of 7 mo, whereas dietary intervention as applied in the STRIP baby project had only a minimal effect.

Relation of plasma phospholipid and cholesterol ester fatty acid composition to carotid artery intima-media thickness: the Atherosclerosis Risk in Communities (ARIC) Study

We examined the relation of fatty acid composition of plasma phospholipids and cholesterol esters with carotid artery intima-media thickness (a measure of atherosclerosis) in 2872 white men and women aged 45-64 y from the Minneapolis center of the Atherosclerosis Risk in Communities Study. In both men and women, average carotid intima-media thickness was associated significantly (P < 0.01) and positively with saturated (SFA) and monounsaturated fatty acid composition, and inversely with polyunsaturated fatty acid (PUFA) composition and the ratio of PUFAs to SFAs in both phospholipids and cholesterol esters. These associations were independent of age, cigarette smoking, low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cholesterol, body mass index, diabetes, and hypertension in men; but in women, only SFAs and PUFAs in the cholesterol esters and the ratio of PUFAs to SFAs were independently associated. The plasma fatty acid pattern is associated with carotid atherosclerosis in a direction generally consistent with the dietary fat-coronary artery disease relation. These results support recommendations to reduce dietary saturated fat to prevent cardiovascular disease.

Milk type during mixed feeding: Contribution to serum cholesterol ester fatty acids in late infancy

Objective: To evaluate the contribution of the type of milk on serum cholesterol ester fatty acids in infants receiving mixed feeding, we analyzed 3-day dietary records and serum cholesterol ester fatty acid composition of 397 seven-month-old infants. Study design: The infants received, in addition to solid food, only one type of milk: human milk (n = 218), a ready-to-use liquid formula (n = 139), a powdered formula (n = 33), or soy formula (n = 7). Results: Mean fat intakes were low and varied from 28% to 31% of energy; the milks provided 43% to 64% of the fat. The mean polyunsaturated/saturated fat ratios of solid foods were from 0.52 to 0.63 and of milks from 0.20 to 0.45. Breast-fed infants' relative serum linoleic acid (18:2n-6) concentration was low (51.2%), whereas infants fed liquid formula had low serum oleic acid (18:1n-9) in accordance with low oleic acid content in that formula. The breast-fed infants had markedly higher serum concentrations of arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) than the infants fed any of the formulas. Conclusion: The typical fatty acid patterns of breast- or formula-fed infants were still evident in 7-month-old infants who already received 60% to 70% of their energy from solid food. Marked differences were seen also in the relative concentrations of docosahexaenoic acid and arachidonic acid despite their small contribution in cholesterol esters. (J Pediatr 1997;130:110-6)

The serum cholesterol ester fatty acid composition but not the serum concentration of alpha tocopherol predicts the development of myocardial infarction in 50-year-old men: 19 years follow-up

A low serum tocopherol concentration and a low proportion of linoleic acid in plasma cholesterol esters have been reported to be associated with coronary heart disease. This study was undertaken to evaluate the predictive importance of the serum cholesterol ester fatty acid composition and serum tocopherol concentration in addition to established risk factors for myocardial infarction. The study comprised 2322 fifty-year-old men who participated in a health survey in 1970–1973 regarding risk factors for coronary heart disease. The proportions of myristic, palmitic, palmitoleic, and dihomogammalinolenic acid were significantly higher in 1970–1973 in subjects who suffered myocardial infarction during the following 19 years, while the proportion of linoleic acid was lower, than in those who remained healthy. Serum tocopherol did not differ significantly between the groups. LDL HDL ratio, systolic blood pressure, and arachidonic acid/dihomogammalinolenic acid ratio were significant independent discriminators between cases and controls in a stepwise logistic regression analysis. This study suggests that middle-aged men who later develop a myocardial infarction are characterized not only by conventional risk factors but also by an altered fatty acid composition of serum cholesterol esters, with a low arachidonic to dihomogammalinolenic acid ratio, indicating reduced Δ 5 desaturase activity. This may imply that changes in the quality of dietary fat intake, or an altered capacity to metabolize fatty acids in the body, could precede the development of coronary heart disease.

Alterations in surfactant neutral lipid composition during the development of bleomycin-induced pulmonary fibrosis

The purpose of this investigation was to correlate changes in the neutral lipids of pulmonary surfactant with previously observed changes in surfactant phospholipids and lung compliance in the rat model of bleomycin-induced pulmonary fibrosis. Bronchoalveolar lavage fluid (BAL) obtained at 0, 1, 3, 7, 14, 30 and 120 days after transtracheal instillation of bleomycin was used as a source of surfactant lipids. The mean concentration of neutral lipids in normal BAL was 439 nmol/lung and was composed of 55% cholesterol (CHO), 27% cholesterol ester (CE) and 19% free fatty acids (FFA). CHO was elevated at 1 day, reaching a maximum 4-fold increase in concentration at 14 days before subsiding to normal at 120 days. In contrast to CHO, CE and FFA were significantly reduced at 1 day after bleomycin with FFA below detectable levels. However, both these species were twice normal levels at 3–30 days before returning to normal at 120 days. The fatty acid composition of CE did not change; however, unsaturated fatty acids were significantly increased in FFA between 3 and 120 days. The data indicate that there are significant alterations in the neutral lipid composition of pulmonary surfactant at various stages of bleomycin induced lung injury. The significance of these changes are not fully understood; however, the possibility exists that an abnormal surfactant results which in turn affects lung function.

The risk to develop NIDDM is related to the fatty acid composition of the serum cholesterol esters.

This investigation was undertaken to study whether the risk to develop non-insulin-dependent diabetes mellitus (NIDDM) among 50-year-old men during a 10-year follow-up period was related to the fatty acid composition of their serum cholesterol esters. There were highly significant differences in the initial health survey between the fatty acid composition in serum in subjects who remained normoglycemic (n = 1,753) and in those who later developed NIDDM (n = 75). The main differences were that the latter had higher proportions of saturated fatty acids and palmitoleic acid (16:1 omega-7), a low proportion of linoleic acid (18:2 omega-6), and a relatively high content of gamma-linolenic (18:3 omega-6) and dihomo-gamma-linolenic (20:3 omega-6) acids in the serum cholesterol esters. The picture was similar also after adjusting for differences in body mass index. In a logistic model, a high proportion of dihomo-gamma-linolenic acid remained a significant contributor to the development of diabetes, along with the height of the insulin index, the blood glucose concentration at 60 min, and the fasting insulin concentration. The increased risk to develop NIDDM related to the serum cholesterol ester fatty acid composition may be mediated by diet and/or genetic factors.

Comparison of the Effects of Two Diets Rich in Monounsaturated Fatty Acids Differing in their Linoleic/α-Linolenic Acid Ratio on Platelet Aggregation

The effect of dietary linoleic/alpha-linolenic acid ratio on human platelet aggregation in vitro was investigated using low-erucic acid rapeseed oil and high-oleic acid sunflower oil as the major fat sources. In a cross-over study 20 healthy male subjects, average age 29 year (range 20-46 yr), followed experimental rapeseed oil (RO) and Trisun-sunflower oil (TSO) diets after their habitual diet for six weeks. Subjects were provided most of the fat containing foods but were allowed to eat other foods almost freely. Fatty acid compositions of the diets calculated from dietary records were as follows (saturated/monounsaturated/polyunsaturated fatty acids): RO diet 12.4/18.6/8.9% of total energy (en%) (linoleic/alpha-linolenic acid ratio 2.8) and TSO diet 11.8/17.8/8.3 en% (linoleic/alpha-linolenic acid ratio 28), respectively. Plasma cholesterol ester fatty acid composition proved compliance to the experimental diets. Platelet aggregations induced by ADP (1, 2 and 3 microM) or thrombin (0.12, 0.15 and 0.18 NIH/ml) were significantly enhanced and collagen-(1.5, 2.5 and 5.0 micrograms/ml) induced aggregation tended to be enhanced after the TSO diet compared with the RO diet. After the TSO diet platelet aggregation was enhanced from the level of the habitual diets by one thrombin (0.18 NIH/ml), one collagen (1.5 micrograms/ml) and all three ADP concentrations. The diets had no effect on antithrombin III activity. Results show that platelet aggregation in vitro decreases as the ratio of linoleic acid to alpha-linolenic acid decreases in diets rich in monounsaturated fatty acids.

Simple thin-layer chromatographic purification procedure for the determination of cholesterol ester fatty acid compositions

A mild procedure for the purification of methyl esters of the fatty acid components of cholesterol esters, from interfering free cholesterol and other contaminating residues, is described. Methyl esters and free cholesterol are formed during the methylation of cholesterol esters. When co-extracted, cholesterol and other contaminating residues interfere with the methyl esters because minute proportions of these residues tend to elute at the same retention times as palmitoleic and stearic acids, to yield unreliable but significantly higher values for palmitoleic (p less than 0.001) and stearic acids (p less than 0.0001), and correspondingly lower values for oleic acid (p less than 0.0001). Purification of methyl esters by thin-layer chromatography eliminates this problem and yields reliable analysis of cholesterol ester fatty acids, without measurable oxidation of unsaturated fatty acids.

The Partial Ileal Bypass Operation Does Not Cause Essential Fatty Acid Deficiency

Recent studies have indicated that ileal resection may lead to essential fatty acid deficiency, as demonstrated by plasma fatty acid composition. In the present study the serum cholesterol ester fatty acid composition was determined in patients who had undergone a partial ileal bypass operation several years earlier. The mean length of ileal exclusion was 2.0 m (range, 1.4-2.5 m). The patients with ileal bypass had severe bile acid malabsorption and slight fat malabsorption (fecal fat, 16 g/day). The fatty acid composition of serum cholesterol esters in the patients with ileal exclusion was identical with that of matched controls; for example, linoleic acid comprised 58% of the C14-18 fatty acids in the control patients and 61% in the patients with ileal bypass. It is concluded that exclusion of the distal third of a healthy small bowel does not cause essential fatty acid deficiency.

Cholesterol ester-composition of the adrenal glands of rats in various fat-rich diet regimes

Cells of adrenal cortex (AC) contain in about 80-90% cholesterol esters (CE), related to total cholesterol. It is assumed, that dietary fats can influence the composition of CE and hydrolytic activity of AC, leading to disorders in steroid biosynthesis. Results are presented about fatty acid composition of CE of AC from rats, fed with a fat rich diet containing different dietary fats. 5 groups and 2 subgroups of male rats at the age of 11 months were investigated: group K--control; group Oil--sunflower oil + lard; group Sch--lard; group Bu--butter; group Hy--hydrogenated oil: Every 5 animals from groups Oil and Bu were treated with dehydroepiandrosterone. Lipids of AC were extracted and analyzed chromatographically. The content of CE and other lipid classes did not differ among experimental groups and control. Differences in fatty acid composition of AC--CE, however, reflect the composition of dietary fats. Trans-isomers were detected by Ag+-thin layer chromatography. It can be assumed, that physiological barrier against trans-isomers is low. Possibly fat rich diets inhibits utilization of linoleic acid, leading to a deficit of arachidonic acid, which influences prostaglandin synthesis and causes disorders in steroid biosynthesis. Hormone treated animals showed minor differences in fatty acid composition of CE in AC in comparison to control. The results outline, that fat-rich diets with different dietary fats influence the composition of CE in AC.

Long-term effects of a single oral dose of polybrominated biphenyls on serum and liver lipids in rats

Adult (5 months) male Sherman strain rats received a single dose of either 0 or 500 mg polybrominated biphenyls (PBB) in corn oil/kg body weight by stomach tube. After an 18-month recovery period, serum and liver samples were examined. The primary serum lipid response was an increase in cholesterol (both free and esterified) and in total phospholipids. The percentage of esterified cholesterol was not significantly different from that of the controls, and no significant differences in the cholesterol ester fatty acid composition were observed. Serum triglycerides were also unaffected. In the PBB-dosed animals, the total hepatic fatty acids contained significantly less palmitic acid and more stearic acid, consistent with an increase in palmitic acid chain elongation activity. No significant differences could be detected in the n−3 or n−6 acids except for a slight decline in the content of 22:6 ( n−3). Hepatic microsomal phospholipids were slightly higher (per milligram protein) in the PBB-dosed animals, and the cholesterol content was lower. Consequently, the cholesterol-phospholipid ratio was reduced, and microsomes from the latter group appeared to have an altered lipid domain on the basis of steady-state fluorescence anisotropy measurements. In addition, total hepatic thiobarbituric acid-reactive substances (assayed as malondialdehyde) were significantly increased in the PBB-dosed animals. This observation appeared to reflect an increased susceptibility to peroxidative stress in the latter group, probably resulting from reduced membrane antioxidant concentrations. The PBB-dosed rats had significantly lower serum retinol levels and a reduced content of this vitamin in liver microsomes. Microsomes were also deficient in α-tocopherol in the PBB-dosed animals, although serum levels were normal.

Cerebral cortical cholesterol changes in cobalt-induced epilepsy.

The present study was designed to elucidate cerebral cortical cholesterol changes observed earlier in cobalt-induced epilepsy in the rat. This model is produced by insertion of cobalt metal rods into the cerebral cortex. Seven days after implantations of cobalt (or other metals), measurements of cerebral cortical lipid concentrations were made in the direct area of metal implantation (lesion area) and in the nonnecrotic tissue immediately adjacent to the lesion site (adjacent area). The cortical concentration of free cholesterol decreased and the concentrations of cholesterol esters (CE) greatly increased in the adjacent area of rats implanted with epileptogenic metals (cobalt and nickel) but not in those implanted with nonepileptogenic metals (copper and stainless steel). Differences in the fatty acid compositions of CE from plasma and those from cobalt-lesioned cortex indicated that the accumulated CE originated in the brain rather than from the plasma CE pool. A time course study revealed that changes in the cortical concentrations of free and esterified cholesterol precedes the first appearance of epileptiform activity as measured by electrocorticography. The reduction of free cholesterol levels most likely reflects increased cholesterol metabolism in the cobalt-lesioned cortex. A major portion of this free cholesterol appears to be converted to CE, but not to bile acid or neutral sterol (potential products of cholesterol metabolism). The concentration of free fatty acids, the other substrate of CE formation, was decreased in the lesion site. The increased metabolism of cholesterol could not be explained by changes in the activities of CE synthetase and hydrolase(s). Since cholesterol in the brain is found almost exclusively in membranes, it is likely that these sterol changes reflect membrane alterations or disintegration. However, the exact relationship of these changes to the epileptogenic effect of cobalt remains unclear.