Cholesteryl Ester Composition Research Articles

Elevated Triglyceride Content Diminishes the Capacity of High Density Lipoprotein to Deliver Cholesteryl Esters via the Scavenger Receptor Class B Type I (SR-BI)

The selective uptake of high density lipoprotein (HDL) cholesteryl ester (CE) by the scavenger receptor class B type I (SR-BI) is well documented. However, the effect of altered HDL composition, such as occurs in hyperlipidemia, on this important process is not known. This study investigated the impact of variable CE and triglyceride (TG) content on selective uptake. CE selective uptake by Y1 and HepG2 cells was strongly affected by modification of either the CE or TG content of HDL. Importantly, TG, like CE, was selectively taken up by a dose-dependent, saturable process in these cells. As shown by ACTH up-regulation and receptor overexpression experiments, SR-BI mediated the selective uptake of both CE and TG. With in vitro modified HDLs of varying CE and TG composition, the selective uptake of CE and TG was dependent on the abundance of each lipid within the HDL particle. Furthermore, total selective uptake (CE + TG) remained constant, indicating that these lipids competed for cellular uptake. These data support a novel mechanism whereby SR-BI binds HDL and mediates the incorporation of a nonspecific portion of the HDL lipid core. In this way, TG directly affects the ability of HDL to donate CE to cells. Processes that raise the TG/CE ratio of HDL will impair the delivery of CE to cells via this receptor and may compromise the efficiency of sterol balancing pathways such as reverse cholesterol transport.

Fatty acid composition of plasma lipids in HIV‐infected children. Comparison with seroreverters

Children infected with the type‐1 human immunodeficiency virus (HIV) are at risk of nutritional deficiencies leading to an impaired polyunsaturated fatty acid (PUFA) status. The aim of the present study was to compare the PUFA composition of plasma lipid classes (total lipids, phospholipids (PL), cholesteryl esters (CE) and triglycerides) in well‐growing HIV‐infected children with an age‐matched group of HIV‐seroreverter children born to infected mothers. Eighteen HIV children, of both sexes, mean age 4.6 y, most of whom under combined antiretroviral regimen, were compared with 18 seroreverters, mean age 5.4 y, comparable for demographic, anthropometric and dietary characteristics. All children had adequate growth parameters (weight and height>3rd percentile). The plasma fatty acid content was similar in the two groups. HIV seropositive subjects showed lower linoleic acid (LA) levels in all the plasma lipid fractions, with higher 20:3n‐9 and 20:5n‐3 levels in PL and CE. The plasma PL triene/ tetraene ratio (marker of relative LA deficiency) related positively to the viral load and negatively to the blood CD4+ lymphocyte count. Compared to age‐matched seroreverter subjects, HIV‐seropositive children show a lipid fatty acid status suggestive of relative LA deficiency and increased turnover of the PUFA series.

Low density lipoproteins develop resistance to oxidative modification due to inhibition of cholesteryl ester transfer protein by a monoclonal antibody

Although numerous studies have investigated the relationship between cholesteryl ester transfer protein (CETP) and high density lipoprotein (HDL) remodeling, the relationship between CETP and low density lipoproteins (LDL) is still not fully understood. In the present study, we examined the effect of the inhibition of CETP on both LDL oxidation and the uptake of the oxidized LDL, which were made from LDL under condition of CETP inhibition, by macrophages using a monoclonal antibody (mAb) to CETP in incubated plasma. The 6-h incubation of plasma derived from healthy, fasting human subjects led to the transfer of cholesteryl ester (CE) from HDL to VLDL and LDL, and of triglycerides (TG) from VLDL to HDL and LDL. These net mass transfers of neutral lipids among the lipoproteins were eliminated by the mAb. The incubation of plasma either with or without the mAb did not affect the phospholipid compositions in any lipoproteins. As a result, the LDL fractionated from the plasma incubated with the mAb contained significantly less CE and TG in comparison to the LDL fractionated from the plasma incubated without the mAb. The percentage of fatty acid composition of LDL did not differ among the unincubated plasma, the plasma incubated with the mAb, and that incubated without the mAb. When LDL were oxidized with CuSO4, the LDL fractionated from the plasma incubated with the mAb were significantly resistant to the oxidative modification determined by measuring the amount of TBARS and by continuously monitoring the formation of the conjugated dienes, in comparison to the LDL fractionated from the plasma incubated without the mAb. The accumulation of cholesteryl ester of oxidized LDL, which had been oxidized for 2 h with CuSO4, in J774.1 cells also decreased significantly in the LDL fractionated from the plasma incubated with mAb in comparison to the LDL fractionated from the plasma incubated without the mAb. These results indicate that CETP inhibition reduces the composition of CE and TG in LDL and makes the LDL resistant to oxidation. In addition, the uptake of the oxidized LDL, which was made from the LDL under condition of CETP inhibition, by macrophages also decreased. —Sugano, M., S. Sawada, K. Tsuchida, N. Makino, and M. Kamada. Low density lipoproteins develop resistance to oxidative modification due to inhibition of cholesteryl ester transfer protein by a monoclonal antibody.

Effects of a prudent diet containing either lean beef and mutton or fish and skinless chicken on the plasma lipoproteins and fatty acid composition of triacylglycerol and cholesteryl ester of hypercholesterolemic subjects

In this two-phase crossover study, 39 hypercholesterolemic subjects followed a prudent diet with either lean red meat or fish and skinless chicken (treatment groups), and 13 subjects (reference group) followed their habitual diet. Fasting blood samples were analyzed for plasma total cholesterol, triacylglycerol (TAG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein one- and two-cholesterol, apolipoprotein-B, very low density lipoprotein cholesterol, and very low density lipoprotein TAG, and fatty acid composition of plasma TAG and cholesteryl ester (CE). Body mass and blood pressure were determined. Seven-day dietary records were kept once at baseline and twice during the treatment periods. Significant differences were observed in dietary intake between the baseline and treatment diets and between the two treatment diets. HDL-C ( P < 0.05) and diastolic blood pressure ( P < 0.01) were higher in patients on the red meat diet than in those on the chicken-fish diet. No other significant differences in lipoproteins were observed between the effects of the two treatment diets. The linoleic acid (%), eicosapentaenoic acid (%), and the eicosapentaenoic acid/arachidonic acid ratios in TAG and CE were higher ( P < 0.01) in subjects on the chicken-fish diet than in those on the red meat diet. In conclusion, this study showed that the effect of two lipid-lowering diets containing either lean red meat or skinless chicken and fish on the atherogenic lipoproteins did not differ significantly. A prudent diet with skinless chicken and fish, however, had a more favorable effect on the fatty acid composition of the plasma TAG and the CE than did the lean red meat diet.

Dietary Associates of Serum Total, LDL, and HDL Cholesterol and Triglycerides in Patients with Coronary Heart Disease

Background. Diet–lipid associations established in clinical trials have in general been weak or nonexistent in cross-sectional studies within a population. Our objective was to analyze the dietary associates of serum lipids in patients with coronary heart disease (CHD) not using lipid-lowering medication.Methods. Patients with coronary bypass grafting (n = 49), balloon angioplasty (n = 46), acute myocardial infarction (n = 79), and acute myocardial ischemia (n = 79) participated in a survey (EUROASPIRE). Patients were selected from hospital records at least 6 months after hospitalization. Diet was assessed by a food record, a short questionnaire, and fatty acid composition of serum cholesteryl esters (CE).Results. Neither the intake of total fat nor that of saturated, monounsaturated, or polyunsaturated fatty acids was associated with serum lipids. Use of soft margarine on bread (though not in cooking or baking) and high intake of fiber and cereal products were associated with low total cholesterol. Linoleic acid in CE was inversely associated with total cholesterol and triglycerides, and eicosapentaenoic acid was inversely associated with triglycerides and positively associated with HDL cholesterol.Conclusions. In the present study use of soft margarine on bread (though not in cooking or baking) and high intake of fiber and cereal products were associates of lowered serum cholesterol concentrations in CHD patients. Fatty acid composition of CE reflected dietary fatty acid intake involved in cholesterol lowering better than food records.

Effects of dietary supplementation of saturated fatty acids and of n-6 or n-3 polyunsaturated fatty acids on plasma and red blood cell membrane phospholipids and deformability in weanling guinea pigs.

The fatty acid composition of plasma cholesteryl esters, plasma phospholipids, red blood cell (RBC) membrane phosphatidylcholine (corresponding to the outer membrane leaflet), and phosphatidylethanolamine (corresponding to the inner membrane leaflet) was investigated in weanling guinea pigs fed with diets of cacao (saturated fatty acids), sunflower oil [n-6 polyunsaturated fatty acids (PUFA)] or fish oil (n-3 PUFA) for 20 wk. RBC deformation was measured by means of a cell-transit analyzer (filtration) and a cone-plate rheoscope. The contents of saturated fatty acids in plasma phospholipids and RBC membrane leaflets were similar in all three groups. Diets with sunflower oil resulted in a high content of linoleic acid in plasma cholesteryl esters and in the outer leaflet of RBC membranes. Fatty acids of fish oil were mainly incorporated in plasma phospholipids and in the inner leaflet of RBC membranes. The arachidonic acid content was high in all groups in the plasma phospholipids and in the inner leaflet. The n-6 and n-3 PUFA were mainly incorporated in the inner leaflet. In all groups the polyunsaturated/saturated fatty acid ratio and the total PUFA content were similar in the inner RBC membrane. The RBC filtration times and the RBC deformation indices were not affected by the dietary treatment.

Impaired function of lecithin:cholesterol acyltransferase in atherosclerosis-susceptible White Carneau pigeons: possible effects on metabolism of oxidized phospholipids

Although White Carneau (WC) pigeons are known to be more susceptible to atherosclerosis than Show Racer (SR) pigeons, the reasons for this difference are not fully understood. While no major differences are known in the lipoprotein composition, a difference in the cholesteryl ester (CE) composition was reported. However, there is little information on the activity or specificity of lecithin:cholesterol acyltransferase (LCAT), the major source of plasma CE. In order to determine whether the esterification of cholesterol or other functions of LCAT are compromised in WC pigeons, we studied the various reactions catalyzed by LCAT in the two groups. The cholesterol esterification was found to be significantly lower in WC pigeons, whether assayed with exogenous or endogenous substrates. Furthermore, lyso phosphatidylcholine (PC) esterification and oxidized PC hydrolysis, two other reactions carried out by LCAT, were also lower in WC. We found evidence for the presence of an active lysophospholipase in pigeon plasma, and this activity was also lower in WC compared to SR. A significant increase in the FC/PC ratio, another reported atherogenic risk factor, was found in WC plasma. Because of the absence of other hydrolytic enzymes in pigeon plasma, LCAT may play an important role in the metabolism of oxidized PC generated during lipoprotein oxidation, and therefore a decrease in its activity in White Carneau pigeons may contribute to increased risk of atherosclerosis.—Liu, M., R. W. St. Clair, and P. V. Subbaiah. Impaired function of lecithin:cholesterol acyltransferase in atherosclerosis-susceptible White Carneau pigeons: possible effects on metabolism of oxidized phospholipids.

Fatty Acid Composition of Serum Cholesteryl Esters in Young Adults

LEARNING OUTCOME: To describe ethnic and gender differences in serum cholesteryl ester fatty acids in young adults. The composition of fatty acids in serum cholesteryl esters (CE) was analyzed by gas chromatography in 106 young adults (x age=26.5 yrs.) (43 males, 63 females; 63 whites, 43 blacks). A total of 97.4% of the fatty acids in serum CE were explained. The median percentage of fatty acids in serum CE was highest for linoleic (52.5%), followed by oleic (18.4%), palmitic (8.8%), arachadonic (7.5%), palmitoleic (2.8%), and stearic (1.2%); with the remaining percentage being explained by minor fatty acids. Small amounts of lauric acid were detected in only 15 individuals. Significant ethnic and gender differences were observed in the median percentage levels of several fatty acids in serum CE, but, no significant differences were observed in linoleic and linolenic. Whites had significantly (p<.05) higher median percentage levels of myristic (3.0% vs. 2.0%) and dihomo-gamma-linolenic acid (1.3% vs. 1.0%)in serum CE than blacks. In contrast, blacks had significantly higher (p<01) median percentage levels of palmitic (9.4% vs. 8.2%) and oleic (19.8% vs. 17.9%) in serum CE than whites. Males had significantly (p<.05) higher median percentage levels of oleic (19.8% vs. 18.1%) in serum CE than females. The combined saturated fat median percentage levels was significantly (p<.05) higher in females (10.2%) than males (10.0%); and in blacks (10.9%) compared to whites (10.0%). The combined monunsaturated fat median percentage levels was significantly (p< 05) higher in males (22.5%) than females (21.0%). The P/S ratio was significantly (p<.05) higher in whites (6.4) than blacks (5.8). These findings suggest ethnic and gender variations in the fatty acid composition of serum CE.

Impact of solid food on plasma arachidonic and docosahexaenoic acid status of term infants at 8 months of age.

We studied healthy term infants at 6 and 8 months of age to assess the effect of fat-containing solid foods (mashed veal, chicken, and pork provided in ready-to-feed cans) on plasma long-chain polyunsaturated fatty acid (LCP) status. Twenty-one infants were breast-fed and 49 were formula-fed. The fat of the formula contained 16.2% linoleic acid and 2.3% alpha-linolenic acid but no LCPs. The solid-food intake was assessed with a 7-day dietary record. Blood samples were obtained at 6 and 8 months of age, and the fatty acid composition of plasma cholesteryl esters (CE) and phospholipids (PL) were analyzed with capillary gas liquid chromatography. The solid food-derived fat intake was higher in the formula-fed than in the breast-fed group at 6 months, and it increased significantly in both groups (from 0.15 to 0.39 g/kg/day and from 0.24 to 0.43 g/kg/day in breast-fed and formula-fed groups, respectively). The relative plasma concentrations of arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) were significantly lower in the formula-fed than in the breast-fed group at both 6 and 8 months. In the formula-fed group at 8 months, the proportion of solid food-derived fat correlated positively with plasma 20:4n-6, and the mean percentage of PL-20:4n-6 were 8.0% (95% confidence interval, 7.4-8.5) and 9.0% (8.3-9.7) in its lowest and highest quartiles, respectively. In the breast-fed group, solid food-derived fat intake had no effect on plasma 20:4n-6. The two groups were similar in that solid-food fat had no effect on plasma PL- or CE-22:6n-3. In conclusion, the introduction of meat containing solid foods to formula-fed infants increases their plasma 20:4n-6, but not to levels found in breast-fed infants. Further studies are needed to establish an optimal fatty acid composition of solid foods during weaning.

Fatty acid composition in major depression: decreased ω3 fractions in cholesteryl esters and increased [formula omitted] ratio in cholesteryl esters and phospholipids

Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and ω3 essential fatty acid levels and by an increased C20: 4ω6 C20: 5ω3 i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2; C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of ω6 and ω3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios ω6 ω3 and C20:4ω6 C20:5ω3 were calculated. Major depressed subjects had significantly higher C20:4ω6 C20:5ω3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased ω6 ω3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3ω3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total ω3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5ω3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

Comparative studies on the substrate specificity of lecithin:cholesterol acyltransferase towards the molecular species of phosphatidylcholine in the plasma of 14 vertebrates.

Comparative studies indicate that plasma cholesteryl ester (CE) composition is correlated with susceptibility to atherosclerosis. We previously showed that the lecithin:cholesterol acyltransferases (LCATs) of susceptible species such as rabbit, pig, and chicken (group I) differ in their substrate and positional specificities from the LCATs of resistant species such as rat and mouse (group II). However, the relative importance of enzyme specificity and substrate phosphatidylcholine (PC) composition in determining the CE composition is not known. To address this, we analyzed the molecular species composition of plasma PC in the same 14 vertebrates in which we previously studied the CE composition and LCAT specificity. The utilization of native PC species by LCAT was studied by determining the loss of each PC after incubation of plasma at 37 degrees C. The major contributor for LCAT reaction was either 16:0-18:2 PC or 18:0-18:2 PC in all species except dog, in which it was 18:0-20:4 PC. The formation of 20:4 CE correlated more with the consumption of 18:0-20:4 PC in group I, and with the consumption of 16:0-20:4 PC in group II. The group II enzymes exhibited higher selectivity for sn-2-20:4 PCs, whereas the group I enzymes showed preference for sn-2-18:2 PCs. The synthesis of high percentage of 20:4 CE in dog plasma was found to be due to the presence of unusually high concentration of 18:0-20:4 PC, rather than due to enzyme selectivity. These results show that the PC molecular species composition, especially the concentrations of sn-2-20:4 phosphatidylcholines has profound influence on plasma CE composition, and possibly on atherogenic risk.

Dietary nucleotides enhance plasma lecithin cholesterol acyl transferase activity and apolipoprotein A-IV concentration in preterm newborn infants.

The activity of lecithin cholesterol acyl transferase (LCAT), a key enzyme in lipoprotein metabolism, is low in newborn preterm infants. It has been suggested that a normal gastrointestinal function might be necessary to induce a postnatal increase of LCAT activity because apoproteins A-I and A-IV (apoA-I and apoA-IV) synthesized in considerable amounts in the intestine are known activators of LCAT. Dietary nucleotides have been reported to enhance intestinal growth and maturation; therefore, we hypothesized that nucleotide supplementation to formulas for preterm infants may influence LCAT activity. To investigate this hypothesis, two groups of preterm infants were fed either a nucleotide-free formula or a nucleotide-supplemented formula during the first month of life. The plasma LCAT activity, plasma levels of apoA-I and apoA-IV, plasma cholesteryl esters, and plasma fatty acid composition of cholesteryl esters and phospholipids were then determined. Infants receiving nucleotides had higher LCAT activities and apoA-IV levels than those receiving the nucleotide-free formula for a few weeks. The changes in apoA-IV levels were highly correlated with those of the LCAT activities. However, there were no significant correlations between changes in LCAT activity and plasma cholesteryl esters or phospholipids. These findings indicate that nucleotide supplementation to formulas for preterm infants may improve dietary lipid tolerance by enhancing plasma LCAT activity, probably as a result of an increase in apoA-IV plasma concentrations; they also suggest that nucleotides may enhance apoA-IV synthesis in the intestine during the neonatal period.

Effect of milk type on the fatty acid composition of serum cholesteryl esters and serum cholesterol concentration in infants

Effect of milk type on the fatty acid composition of serum cholesteryl esters and serum cholesterol concentration in infants

Analysis of adrenal cholesteryl esters by reversed phase high performance liquid chromatography.

A reversed phase high performance liquid chromatographic (HPLC) method was developed for direct profiling and determination of adrenal cholesteryl ester composition. Cholesteryl adrenate and cholesteryl cervonate, which are not commercially available, were synthesized as markers. Lipid extracts of rat adrenal homogenates or lipid droplets were individually applied to a conditioned silica gel-60 column which separated cholesteryl esters from other native lipids. The eluted cholesteryl ester fraction was then analyzed by HPLC. With cholesteryl heptadecanoate as internal standard, seven adrenal cholesteryl esters were detected and quantified: cholesteryl cervonate, cholesteryl arachidonate, cholesteryl adrenate, cholesteryl myristate, cholesteryl oleate, cholesteryl palmitate, and cholesteryl stearate. Among them, cholesteryl adrenate appeared to be the major sterol ester stored in the rat adrenal.

Cholesteryl esters on the body surfaces of the camel tick, Hyalomma dromedarii (Koch, 1844) and the brown dog tick, Rhipicephalus sanguineus (Latreille, 1806)

Cholesteryl esters were found to constitute a major component of the lipids coating the body cuticle of females of the camel tick, Hyalomma dromedarii and the brown dog tick, Rhipicephalus sanguineus. One or more cholesteryl esters, alone or in combination, have been shown to serve as the mounting sex pheromone of several species of ixodid ticks. Consequently, knowledge of these compounds is important for an understanding of the mating behavior of these ticks. Based on thin layer chromatography, cholesterol and cholesteryl esters were the most abundant neutral lipids found on the body surfaces of fed females of these two species. Analysis using HPLC demonstrated significant quantities of the following compounds, tentatively identified as cholesteryl esters (expressed in micrograms per female equivalent), in H. dromedarii: Cholesteryl acetate 18.2; cholesteryl laurate, 6.8; cholesteryl linoleate, 24.8; cholesteryl oleate, 12.9; cholesteryl palmitate, 0.3; and cholesteryl stearate 1.7. In contrast, the same method revealed only 3 cholesteryl esters in extracts of females of R. sanguineus: Cholesteryl acetate, 2.0; cholesteryl linoleate, 8.5; and cholesteryl oleate, 3.0. In both species, two unidentified peaks, with the spectral characteristics of cholesteryl esters, were also observed. Identification of the cholesteryl esters was confirmed: by (1) positive bioassay results with conspecific (H. dromedarii) males and heterospecific (Dermacentor variabilis) males; (2) similarity of ultraviolet spectra between identified sample peaks and authentic standards; and (3) demonstration of cholesterol and the corresponding free fatty acid following enzymatic digestion of each of the HPLC-separated fractions containing the different cholesteryl esters. Comparisons with the cholesteryl ester composition of the mounting sex pheromone of other metastriate Ixodidae are discussed. These findings, along with studies reported previously, suggest that differences in the mounting sex pheromones of ixodid ticks are an important factor in minimizing heterospecific matings in nature.

Effect of Administration of Gamma-Linolenic Acid on the Fatty Acid Composition of Serum Phospholipids and Cholesteryl Esters in Patients with Cystic Fibrosis

This study examined the effects of supplementing patients with cystic fibrosis daily for 4 weeks with 1,500 mg borage oil, containing 330 mg gamma-linolenic acid, on the fatty acid composition of serum phospholipids (PL) and cholesteryl esters (CE). Vital capacity and forced expiratory volume in 1 s were also measured before and after treatment. In serum PL the content of arachidonic acid (AA) increased and that of palmitic acid decreased significantly after borage oil administration. In serum CE dihomogamma-linolenic acid increased whereas docosahexaenoic acid decreased significantly. In this lipid class, AA and the sum of AA plus its precursor, dihomogamma-linolenic acid, increased significantly with the dose fed. A positive correlation was found between change in vital capacity and change in linoleic acid content of serum CE and AA content of serum PL.

Influences of postnatal age and dietary nucleotides on plasma fatty acids in the weanling rat.

Dietary nucleotides seem to play a number of physiologic roles during early life. They are improved in the maintenance of the immune system, intestinal maturation, and lipid metabolism. Nucleotides affect the conversion of essential fatty acids into their long-chain polyunsaturated (PUFA) derivatives in both preterm and at-term newborn infants. This work examines the effect of postnatal age and dietary nucleotides on the fatty acid composition of total plasma lipids and lipid fractions in the rat. Weanling rats (21 days old) were divided into three groups. The first group was killed, and the other two groups were fed a standard semipurified diet, and the same diet supplemented with 250 mg each of CMP, UMP, AMP, GMP, and IMP per 100 g of diet for 4 weeks. Advancing postnatal age led to an increase of total plasma fatty acids, especially saturated, and PUFA of the n-6 series, whereas PUFA of the n-3 series decreased. The fatty acid profile of plasma phospholipids (PL) exhibited minor changes, although there was a tendency to show lower levels of saturates and PUFA of the n-3 series and increased levels of PUFA of the n-6 series. Cholesteryl esters showed a response similar to that of PL, although the increase in arachidonic acid (20:4n-6) was significant. For triglycerides, linoleic acid (18:2n-6) and monounsaturates increased their levels, whereas saturates decreased. Dietary nucleotides mediated a significant increase in total plasma fatty acids, namely monounsaturated fatty acids and PUFA of both n-6 and n-3 series as compared with the control group. The relative fatty acid composition of PL and cholesteryl esters was mostly unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of acute hyperinsulinemia on fatty acid composition of serum lipids in non-insulin-dependent diabetics and healthy men

The fatty acid pattern of serum phospholipids, cholesteryl esters, triglycerides and free fatty acids was measured before and after a 5-h two-step euglycemic hyperinsulinemic clamp (75 and 1400 μU/ml) in 21 non-insulin-dependent diabetics and 14 age-, weight-, and sex-matched healthy controls. Acute hyperinsulinemia was associated with a statistically significant increase in essential fatty acid and a decrease in non-essential fatty acid contents in triglycerides while the levels of serum triglycerides and free fatty acids dropped in both groups. The fatty acid composition of phospholipids and cholesteryl esters remained unchanged as did the levels of serum phospholipids, total cholesterol and HDL cholesterol.

Effect of apolipoprotein activators on the specificity of lecithin:cholesterol acyltransferase: determination of cholesteryl esters formed in A-I/C-III deficiency.

Although it is known that plasma lecithin:cholesterol acyltransferase (LCAT) is activated by several apolipoproteins (apo) including A-I, C-I, D, A-IV, and E, it is not clear what the physiological importance of having different apolipoprotein activators is. One possible explanation is that the activation by different apolipoproteins may result in the utilization of different species of phosphatidylcholine (PC), leading to the formation of different species of cholesteryl esters (CE). In order to determine this possibility, we analyzed the molecular species composition of PC and CE in two patients with familial deficiency of apoA-I and apoC-III. The LCAT activity, assayed by three different procedures, was found to be 36-63% of the control value. The lower LCAT activity, however, was due to deficiency of the enzyme rather than the absence of apoA-I. The patients' plasma was relatively enriched with sn-2 18:2 PC species reflecting the partial deficiency of LCAT activity. The fatty acid composition of plasma CE was not significantly different from that of controls. HPLC analysis of labeled CE formed after incubation of plasma with [C14]cholesterol showed no significant difference in the species of CE synthesized by the LCAT reaction. The transfer of pre-existing as well as newly formed CE from HDL to the apoB-containing lipoproteins was accelerated compared to control plasma. These results show that the absence of apoA-I does not significantly affect either the activity or the specificity of LCAT, and that the other apolipoprotein activators can substitute adequately for it.

High levels of cholesteryl esters, progesterone and estradiol in the testis of aging male fischer 344 rats: Feminizing leydig cell tumors.

The levels and fatty acid composition of cholesteryl esters (CEs), and the levels of steroid hormones in the testis of aging Fischer 344 (F344) rats were studied in comparison with those of 6-month-old rats without Leydig cell tumors (controls). The total lipid content in the testis increased as Leydig cell tumors developed: in 23-month-old rats, the content increased to five times higher than that of the controls. The CE level reached about 300 times higher than that of the controls and comprised 57.5% of the total lipid of the testis. The fatty acid composition of the CEs in the tumor compared to the normal tissue from the controls was characterized by a marked increase in 22:4 (n-6) and a decrease in 22:5 (n-6), a characteristic acid in rat testis lipids. Testicular progesterone levels considerably increased with the development of tumors (23-month-old rats, 2870 ng/wet wt; controls, 7 ng/g wet wt). Also, levels of estradiol showed striking increments (23-month-old rats, 2205 pg/g wet wt; controls, 153 pg/g wet wt). On the other hand, testosterone levels decreased (23-month-old rats, 13 ng/g wet wt; controls, 50 ng/g wet wt). These results suggest that Leydig cell tumors in aging F344 rats resemble the ovary tissue of rats in the levels and fatty acid composition of the CEs, and in the levels of steroid hormones. This is supported by the observation that the two kinds of cells found in the tumor tissue resemble cells of the corpus luteum and granulosa cells of the follicles, respectively, in the ovary of rats. In conclusion, the study shows that Leydig cell tumors in aging male F344 rats have a tendency towards feminization.