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PubMed2006

The hypertriglyceridemic clamp technique. Studies using long-chain and structured triglyceride emulsions in healthy subjects.

In a randomized crossover study, plasma kinetics of 2 different types of fat emulsions were studied in 8 healthy volunteers by using a hypertriglyceridemic clamp technique. The method involves the stabilization of serum triglyceride (TG) concentration during 180 minutes at a predetermined level (4 mmol/L) by adjustment of TG infusion rate by repeated online measurements of serum TG concentration. The fat emulsions under study were a long-chain fatty acid triglyceride (LCT) emulsion (Intralipid 20%, Fresenius Kabi, Sweden) and a structured triglyceride (STG) emulsion (Structolipid 20%, Fresenius Kabi) where medium- and long-chain fatty acids have been interesterified within a TG molecule. The hypertriglyceridemic clamp was found to have acceptable reproducibility when tested in 3 healthy individuals on 2 different occasions, as similar steady-state TG levels were obtained by infusing similar amounts of fat. The average (+/-SEM) TG concentration during the 180-minute clamp was similar for STGs and LCTs (4.0 +/- 0.1 vs 3.9 +/- 0.1 mmol/L; not significant), but the amount of fat that had to be infused was significantly higher during STG than during LCT clamping (0.31 +/- 0.04 vs 0.21 +/- 0.02 g TG per minute; P < .05). Higher serum levels of free fatty acids (1.80 +/- 0.13 vs 0.96 +/- 0.09 mmol/L; P < .05), free glycerol (1.30 +/- 0.07 vs 0.76 +/- 0.08 mmol/L; P < .001), and beta-OH butyrate (1.61 +/- 0.44 vs 1.17 +/- 0.23 mmol/L; not significant) were obtained at the end of the clamp during infusion of STGs compared with LCTs. During infusion of STGs the medium-chain fatty acids octanoic (C:8) and decanoic acid (C:10) constituted approximately half of circulating fatty acids that correspond to the compositional ratio of the emulsion. Plasma lipoprotein lipase (LPL) concentration was higher during STG than during LCT clamping (6.06 +/- 0.62 vs 3.15 +/- 0.40 mU/mL; P < .05), and there was a positive correlation between the mean LPL concentration and the amount of infused TG during the steady-state period (r = 0.58; P < .05). In conclusion, the hypertriglyceridemic clamp method was found to give reproducible results and could be considered for comparison of metabolic clearance properties of different types of fat emulsions. The capacity of healthy subjects to eliminate STGs from blood was greater than for LCTs. An increased LPL activity induced by the higher TG infusion rate may have contributed to the increased metabolic clearance of STGs.

Adult↗
PubMed2006

Decrease in blood triglycerides associated with the consumption of eggs of hens fed with food supplemented with fish oil.

BACKGROUND: n-3 polyunsaturated fatty acids (n-3 PUFA) convey several health benefits, including a reduction of serum concentration of triglycerides (TG). AIM: To examine the effect on blood lipids, particularly TG, of a diet with n-3 PUFA enriched eggs in healthy volunteers in the Seychelles (Indian Ocean). METHODS: Double-blind crossover trial with one group of volunteers fed with 5 normal eggs per week during 3 weeks followed by 5 enriched eggs per week during the next 3 weeks while the other group received eggs in the inverse sequence. Hen feed was supplemented at 5% with tuna oil. Enriched eggs contained nine times more n-3 PUFA than usual eggs (mainly docosahexaenoic acid). RESULTS: Twenty-five healthy volunteers participated in the study. Based on pooled results observed during the two 3-week periods, consumption of enriched eggs was associated with a significant 16-18% decrease in serum triglycerides (P<0.01) but with no significant difference in serum LDL-cholesterol and HDL-cholesterol. Serum LDL-cholesterol increased during the first 3-week period and decreased during the second 3-week period with both normal and enriched eggs. Participants did not report a systematic preference for either type of eggs. CONCLUSIONS: Reasonable consumption of n-3 PUFA enriched eggs was associated with a significant decrease in serum triglycerides. These eggs could be a palatably acceptable source of n-3 PUFA.

Adult↗
PubMed2000

Low-density lipoprotein particle size, triglycerides, and high-density lipoprotein cholesterol as risk factors for coronary heart disease in older Japanese-American men.

Decreased low-density lipoprotein (LDL) particle size is associated with coronary heart disease (CHD) risk among middle-aged Caucasian populations, and has been consistently correlated with increased plasma levels of triglyceride and decreased levels of high-density lipoprotein (HDL) cholesterol. This study examines whether these risk factors predict CHD among older Japanese-American men. With use of the Honolulu Heart Program Lipoprotein Exam 3 (1980 to 1982) as baseline, and 12-year follow-up for CHD events, a nested, case-control study was designed. One hundred forty-five incident CHD cases were identified and matched to 2 controls each. LDL particle diameter (size) was determined by gradient gel electrophoresis. A 10-angstrom (A) decrease in LDL size at baseline was associated with increased risk of incident CHD (relative risk 1.28, 95% confidence interval 1.01 to 1.63). After adjustment for baseline risk factors, the LDL size association was no longer statistically significant (relative risk 1.13, 95% confidence interval 0.86 to 1.49). When principal components analysis was used to define a composite variable for LDL size, triglycerides, and HDL cholesterol, this component predicted CHD independent of smoking, alcohol consumption, physical activity, body mass index, hypertension, diabetes, and beta-blocker use (p <0.01). Therefore, this prospective analysis of data from older, Japanese-American men demonstrated that decreased LDL size is a univariate predictor of incident CHD, and that a composite risk factor of LDL size, triglyceride, and HDL cholesterol was a risk factor for CHD independent of other risk factors.

Aged↗
PubMed1998

Serum triglycerides and clinical benefit in lipid-lowering trials.

Trial evidence shows that effective lowering of serum total cholesterol and particularly of low-density lipoprotein (LDL) cholesterol is important for the prevention of total mortality, coronary artery disease mortality, and major coronary events. The role of serum triglyceride reduction in achieving clinical benefit is unclear and poorly documented. On the other hand, no specific trials have studied the importance of triglyceride lowering among patients with marked hypertriglyceridemia. One of the problems in assessing patients with high serum triglyceride levels may be the heterogeneous background of the molecular mechanisms that result in hypertriglyceridemia.

Anticholesteremic Agents↗
PubMed1982

Effects of oral contraceptives on lipoprotein triglyceride and cholesterol: relationships to estrogen and progestin potency.

Hormone formulation and estrogen/progestin potency were evaluated in relation to triglyceride and cholesterol concentrations in total plasma and lipoprotein fractions and in relation to lipid composition among a random sample of female telephone company personnel. Triglyceride concentrations in whole plasma, very low-density lipoprotein, and high-density lipoprotein (HDL) were elevated in response to increasing estrogen potency as were triglyceride concentrations in low-density lipoprotein (LDL). LDL cholesterol rose with increasing estrogen potency in contraceptive users but was slightly lower in postmenopausal estrogen-treated women. Plasma HDL cholesterol varied according to estrogen and progestin levels. The LDL cholesterol/triglyceride ratio was reduced for all combination oral contraceptives examined. Sequential oral contraceptives of postmenopausal estrogens did not significantly alter the cholesterol/triglyceride ratio in any lipoprotein fraction. Potential arteriosclerotic risk from sex hormone use may vary among oral contraceptive formulations.

Adult↗
PubMed1988

Macrophage cholesterol removal by triglyceride-phospholipid emulsions.

Phospholipid liposomes were previously shown to mobilize cholesterol from cultured macrophage foam cells. Because Intralipid, a clinically available triglyceride-phospholipid emulsion, contains both phospholipid liposomes and triglyceride-emulsion particles, we sought to study its effect on macrophage cholesterol mobilization. Following an 18h incubation of J774 macrophages in serum-free medium supplemented with Intralipid, cholesteryl ester content decreased by up to 50% in previously cholesterol-loaded cells, and by 25% in non-loaded cells. Both components of Intralipid, liposomes and emulsion particles, independently caused reductions in cellular cholesteryl ester. We conclude that clinically available triglyceride-phospholipid emulsions can mobilize macrophage cholesterol in vitro.

Animals↗
PubMed2003

Appropriateness of cholesterol and triglycerides reporting checked by External Quality Assessment programs.

BACKGROUND: The recommendations of the Second Joint Task Force of European and Other Societies on Coronary Prevention and the third Adult Treatment Panel report (ATPIII) released by the National Cholesterol Education Program are based on accumulating evidence concerning the contribution of lipoproteins and other risk factors in the development of coronary heart disease (CHD). The laboratories play an important role in the successful adoption of these guidelines. METHODS: In External Quality Assessment (EQA) programs managed by the Center of Biomedical Research, results and respective reference intervals (RI) are sent as laboratory's medical form. We assessed how well the 200 participants to EQA scheme 2002 for clinical biochemistry reported total cholesterol (TC) and triglycerides (TGs) results according to either European or National Cholesterol Education Program (NCEP) guidelines. RESULTS: Only 18% of laboratories reported total cholesterol concentrations correctly in terms of desirable, borderline-high, and high risk for the CHD development, 12% reported a single desirable value (180, 190, or 200 mg/dl), and 70% reported the RI (85 laboratories in the whole interval, 34 are the only upper reference limit and 15 are the desirable value in addition to RI). The upper reference limit was 200 mg/dl in 65% of cases, but 32% of laboratories presented higher limits, reaching values as high as 250-260 mg/dl. Only the 3.7% of laboratories reported triglyceride concentrations in terms of risk-oriented ranges for the CHD development, 6.8% the single desirable value, and 89.5% the RI. CONCLUSION: Our study demonstrates that the current practice of reporting results for cholesterol and triglycerides does not follow the guidelines, and appropriate changes are required to be made.

Cholesterol↗
PubMed1998

VLDL compositional changes and plasma levels of triglycerides and high density lipoprotein.

VLDL chemical composition is related to plasma levels of triglycerides and HDL-cholesterol. We evaluated patients with primary hypertriglyceridemia with or without hypoalphalipoproteinemia and subjects with normotriglyceridemia with hypoalphalipoproteinemia. The pattern observed in all the groups was an enrichment in the triglyceride content of VLDL and in apo B-VLDL. Compared to controls, LpC-III:B levels were higher in hypertriglyceridemic patients with low or normal HDL-cholesterol levels (7.3 +/- 0.6 vs. 14.9 +/- 1.8 and 12.3 +/- 2.8 mg/dl; P < 0.005 and P < 0.01, respectively) and LpE:B concentration was only increased in patients with hypertriglyceridemia and normal HDL-cholesterol levels (3.1 +/- 0.5 vs. 6.3 +/- 1.0 mg/dl; P < 0.01). The activity of the cholesteryl ester transfer protein was higher in hypertriglyceridemic patients with low HDL-cholesterol levels than in controls (380 +/- 25 vs. 262 +/- 14% cholesteryl esters/ml.h; P < 0.001). The most atypical VLDL particle was found in patients who combined an accumulation of VLDL particles and a reduction in HDL-cholesterol concentration. These two parameters represent both ends of the cholesteryl ester-triglyceride transfer, a crucial factor for VLDL chemical composition and HDL levels.

Adult↗
PubMed2003

Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity.

Hypertriglyceridemia, low plasma concentrations of high density lipoproteins (HDL) and qualitative changes in low density lipoproteins (LDL) comprise the typical dyslipidemia of insulin resistant states and type 2 diabetes. Although isolated low plasma HDL-cholesterol (HDL-c) and apolipoprotein A-I (apo A-I, the major apolipoprotein component of HDL) can occur in the absence of hypertriglyceridemia or any other features of insulin resistance, the majority of cases in which HDL-c is low are closely linked with other clinical features of insulin resistance and hypertriglyceridemia. We and others have postulated that triglyceride enrichment of HDL particles secondary to enhanced CETP-mediated exchange of triglycerides and cholesteryl ester between HDL and triglyceride-rich lipoproteins, combined with the lipolytic action of hepatic lipase (HL), are driving forces in the reduction of plasma HDL-c and apoA-I plasma concentrations. The present review focuses on these metabolic alterations in insulin resistant states and their important contributions to the reduction of HDL-c and HDL-apoA-I plasma concentrations.

Animals↗
PubMed1987

A method for the sequential colorimetric determination of serum triglycerides and cholesterol.

A simple spectrophotometric method for the sequential determination of triglycerides and cholesterol from a single serum sample was developed. In this two-stage procedure, the triglycerides and cholesterol esters are first hydrolysed to glycerol and free cholesterol respectively, with simultaneous scavenging of the liberated free fatty acids, a technique that ensures clarity of the sample. The glycerol is subsequently reacted to result in an intense red chromogen with a peak absorption maximum at 510 nm following a series of enzymic reactions. In the second stage, addition of cholesterol oxidase leads to oxidation of free cholesterol generated from the cholesterol esters in the first stage and the free cholesterol normally present in the sample, yielding in a similar fashion the identical red chromogen whose absorbance is also measured at 510 nm. Results obtained with the proposed method demonstrate good correlation with established individual procedures for triglycerides and cholesterol.

Bilirubin↗
PubMed1996

Association of lipoprotein cholesterol and triglycerides with the severity of coronary artery disease in men and women.

The differences between the lipid profiles of male and female patients and the effect of plasma lipids on the extent of coronary artery disease were evaluated in 122 angiographically assessed coronary artery disease patients (95 males and 27 females) and 60 controls. Both male and female patients had lower HDL-cholesterol and higher total cholesterol, LDL-cholesterol, triglyceride, VLDL-cholesterol and VLDL-triglyceride concentrations than the controls. The VLDL lipid values did not differ significantly between the male patients with different extent of CAD, whereas the VLDL lipid values of female patients tended to increase with an increasing severity of CAD. High Lp(a) (> or = 35 mg/dl) values were more prevalent in patients with > 50% coronary stenosis compared to patients with < 50% stenosis and the controls (29%, 17% and 12%, respectively). The apolipoprotein E phenotypes and epsilon allele frequencies were similar in the patients and the controls. Low HDL-cholesterol and high LDL-cholesterol are CAD risk factors for both sexes. For women, elevated VLDL-triglycerides seem to be an additional risk factor for CAD.

Adult↗
PubMed1997

Increased J774 macrophage cytotoxicity of late postprandial triglyceride-rich lipoproteins from normolipidemic young men expressing an apolipoprotein epsilon 4 allele.

It has been demonstrated that normolipidemic young men with apolipoprotein E4/3 phenotype have a prolonged postprandial clearance of triglyceride-rich lipoproteins following a high-fat diet. In the present study, we isolated fasting and postprandial (3 and 8 h) lipoprotein fraction from normolipidemic young men with E3/3 and E4/3 phenotypes and examined the in vitro cytotoxicity of these lipoproteins towards J774 macrophages. 8 h E4/3 very low density lipoprotein (VLDL) were significantly more cytotoxic than either 8 h E3/3 VLDL or fasting and 3 h E4/3 VLDL (lactate dehydrogenase (LDH) released: 161 +/- 21, 107 +/- 9, 88 +/- 16 and 101 +/- 12 I.U./l, respectively). Fasting E4/3 intermediate density lipoprotein (IDL) were also significantly more cytotoxic than either fasting E3/3 IDL or 3 h and 8 h E4/3 IDL (LDH released: 105 +/- 23, 60 +/- 9, 37 +/- 5 and 53 +/- 16 I.U./l, respectively), whereas either fasting or postprandial low density lipoprotein (LDL) and high density lipoprotein (HDL) samples did not show any difference in cytotoxicity between the two groups studied. 8 h E4/3 VLDL samples incubated with J774 macrophages had a lower esterified cholesterol (40 +/- 3 versus 52 +/- 3 micrograms), and higher triglyceride (783 +/- 133 versus 418 +/- 64 micrograms) and free fatty acid (FFA) (2.0 +/- 0.4 versus 0.9 +/- 0.1 microgram) content than fasting E4/3 VLDL. The increased macrophage cytotoxicity of late postprandial triglyceride-rich lipoproteins seems to be related to the FFA content of E4/3 VLDL.

Adult↗
PubMed2000

Cytosolic triglycerides and oxidative stress in central obesity: the missing link between excessive atherosclerosis, endothelial dysfunction, and beta-cell failure?

Central obesity is increasingly recognized as a risk factor for atherosclerosis and type 2 diabetes mellitus. Here we present a hypothesis that may explain the excess atherosclerosis, endothelial dysfunction and progressive beta-cell failure. Central obesity is associated with increased cytosolic triglyceride stores in non-adipose tissues such as muscles, liver and pancreatic beta-cells. A high cytosolic triglyceride content is accompanied by elevated concentrations of cytosolic long-chain acyl-CoA esters, the metabolically active form of fatty acids. These esters inhibit mitochondrial adenine nucleotide translocators, resulting in an intramitochondrial ADP deficiency. In vitro, such ADP deficiency is a potent stimulator of mitochondrial oxygen free radical production, and we assume that this mechanism is also active in vivo. The decline of organ function with normal ageing is thought to be due, at least partly, to a continuous low-grade mitochondrial oxygen free radical production. In tissues containing increased cytosolic triglyceride stores this process will be accelerated. Tissues with a high-energy demand or poor free radical scavenging capacity, such as pancreatic beta-cells, are likely to be more susceptible to this process. This is how we explain their gradual dysfunctioning in central obesity. Likewise we propose that the enhanced production of oxygen free radicals in endothelial cells, or vascular smooth muscle cells, leads to the increased subendothelial oxidation of LDL and atherosclerosis, as well as to the endothelial dysfunction and microalbuminuria.

Animals↗
PubMed1981

Improved separation of triglycerides at low temperatures by reversed-phase liquid chromatography.

A high-performance liquid chromatographic technique for the separation of triglycerides in natural mixtures is described. The influence of column temperature on separation is investigated, and a linear relationship between log k' and 1/T is demonstrated. Operating this reversed-phase technique with a LiChrosorb RP-18 packing at 14.5 degree C, separation of triglycerides with the same equivalent carbon numbers (ECN), but different degrees of saturation, is obtained. The composition of an eluent which permits separation of saturated triglycerides with carbon numbers as high as 54 (e.g., tristearin) is given.

Chromatography, High Pressure Liquid↗
PubMed1985

Evaluation of the mass detector for quantitative detection of triglycerides and fatty acid methyl esters.

The mass detector, a light scattering detector for use with high-performance liquid chromatography systems, was studied in order to determine which factors might affect sensitivity and quantification in the determination of triglycerides and other lipid materials. The detector response was found to be non-linear for triglycerides. The sensitivity was not only affected by evaporation temperatures and atomiser inlet air pressures within the detector, but also by the mobile phase flow-rate, and its composition. Detection limits of less than 1 microgram were achieved for non-volatile, saturated triglycerides, by direct injection, and the reproducibility of responses was about +/- 6% with isocratic elution (excluding tributyrin which was too volatile to be quantified accurately), but somewhat greater (+/- 16%) with gradient elution.

Butter↗
PubMed2002

Characterization of triglycerides in vegetable oils by silver-ion packed-column supercritical fluid chromatography coupled to mass spectroscopy with atmospheric pressure chemical ionization and coordination ion spray.

Characterization of triglycerides in vegetable oils was achieved by silver-ion packed-column supercritical fluid chromatography (SI-pSFC) with mass spectrometric detection. Hyphenation was made using commercially available liquid chromatography-mass spectrometry (LC-MS) interfaces without any modification. A make-up fluid was delivered through a T-piece placed before or after the SFC restrictor by means of a high pressure pump. Atmospheric pressure chemical ionization (APCI) and coordination ion spray (CIS) with silver ions were used as ionization modes. Compared to UV detection, the sensitivity was increased by a factor of 100. Both ionization modes are generating similar structural information. Molecular ions [M-H]+ or [M-Ag(-)] are observed in the mass spectra with exception of the saturated triglycerides for which only CIS gives intense molecular ions. The position at which the fatty acids are esterified to the glycerol backbone can be elucidated by pSFC-APCI although it remains speculative whether this is valid for highly unsaturated triglycerides because reference compounds are not available to proof this.

Atmospheric Pressure↗
PubMed1986

Energy balance in low birth weight infants fed formula of high or low medium-chain triglyceride content.

We tested the effect on energy balance of the partial substitution of medium-chain for long-chain triglycerides in the diet of growing low birth weight infants. Fifteen infants were studied in a randomized double-blind crossover clinical trial in which each infant was fed each of two formulas, which were of equal gross energy and protein content but differed in fat composition. The high medium-chain triglyceride (MCT) formula contained medium- and long-chain triglycerides in a weight/weight ratio of 46:54; in the low MCT formula the ratio was 4:96. The hypothesis tested was that under conditions of equal gross energy intake the two diets would differ in their digestible and metabolizable energy contents and would produce differences in the infants' rates of energy expenditure and energy storage. Gross energy intakes averaged 562 and 555 kJ/kg/day (134 and 133 kcal/kg/day) with the high and low MCT formulas, respectively. With each diet, coefficients of energy digestibility (0.93) and metabolizability (0.91) were identical; the rates of energy expenditure were 262 (high MCT) and 265 (low MCT) kJ/kg/day (63 kcal/kg/day for both diets), and of energy storage were 246 (high MCT) and 239 (low MCT) kJ/kg/day (59 and 57 kcal/day). These differences were not significant. There were also no significant differences between the two diets in coefficients of nitrogen retention (mean 0.70) or in rate of weight gain (mean 21.5 gm/kg/day). The use of high MCT content in infant formula neither provided a nutritional advantage in energy digestibility or metabolizability nor resulted in an increased rate of energy expenditure or of energy storage.

Body Weight↗
PubMed1994

Epidemiology of triglycerides, small dense low-density lipoprotein, and lipoprotein(a) as risk factors for coronary heart disease.

In addition to LDL cholesterol, triglyceride; small, dense LDL (LDL subclass phenotype B); and lipoprotein(a) are emerging as important risk factors for CHD. Elevated plasma levels of each of these risk factors have consistently been associated with increased risk of CHD in case-control studies of white patients. In prospective studies, however, the association between triglycerides and CHD is generally not independent of HDL cholesterol in multivariate statistical analyses. Although the data are scarce, studies in women show that triglycerides are a stronger risk factor for CHD in women than in men. Although no prospective studies of LDL subclass phenotype B have been reported, a number of potential atherogenic mechanisms may be responsible for the association with CHD seen in the case-control studies. Similarly, few prospective studies of lipoprotein(a) have been published, all in Scandinavian men. The observational studies generally show an association between elevated lipoprotein(a) and CHD in whites but not in blacks. Each of these risk factors also has a genetic component. Of the two familial forms of hypertriglyceridemia, FCH has been associated with familial CHD in two cross-sectional studies. LDL subclass phenotype B is inherited consistent with a single major gene effect, and candidate gene linkage studies are in progress to map the chromosomal location of this proposed gene. Finally, lipoprotein(a) levels are largely attributable to variation at the apo(a) locus on chromosome 6. Whether other genetic variations explain the lack of reported associations between lipoprotein(a) and CHD in black populations remains to be determined. Understanding of these "non-LDL" lipoprotein-related risk factors will provide important information for the development of new, effective intervention strategies for the prevention of CHD.

Arteriosclerosis↗