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Myocardial triglycerides and systolic function in humans: in vivo evaluation by localized proton spectroscopy and cardiac imaging.

Recent experimental data suggest that adiposity directly damages the heart by promoting ectopic deposition of triglyceride, a process known as myocardial steatosis. The goal of this study was to develop and validate proton magnetic resonance spectroscopy ((1)H MRS) as an in vivo tool to measure myocardial lipid content. Complementary studies in rat tissue ex vivo and in 15 healthy humans in vivo provided evidence that (1)H MRS constitutes a reproducible technique for the measurement of myocardial triglyceride. In myocardial tissue from Zucker rats, the (1)H MRS measurement of triglyceride matched that obtained by biochemical measurement (P < 0.001). In human subjects triglyceride was evident in the hearts of even the very lean individuals and was elevated in overweight and obese subjects. Increased myocardial triglyceride content was accompanied by elevated LV mass and suppressed septal wall thickening as measured by cardiac imaging.

Animals↗

Sequential determination of triglycerides and free fatty acids in biological fluids by use of a continuous pretreatment module coupled to a gas chromatograph.

A continuous system coupled to a gas-liquid chromatograph was used for the sequential determination of triglycerides and free fatty acids in serum and urine. The module provides compositional information and hence more detailed information on lipid metabolism changes in patients suffering metabolic disorders. Lipids in biological samples are manually extracted in methanol-n-hexane and introduced into the flow system; free fatty acids are then separated by retention on an ion-exchange resin and triglycerides (not retained) are transesterified with acetyl chloride in methanol. The resulting methyl esters are continuously injected into the gas chromatograph and determined by using a flame ionization detector. In a second step, retained free fatty acids are eluted and derivatized (also with acetyl chloride in methanol) and subsequently determined similarly as the triglycerides. The proposed method was applied to the determination of triglycerides in a lipid control serum; free fatty acids were determined in a human pool serum by the proposed method and compared with the volumetric method used in clinical practice. The results obtained in both instances showed good agreement between the results provided for triglycerides and free fatty acids. The proposed method was also applied to urine samples; a parallel recovery study was also made in order to assess the performance of the method.

Automation↗

The importance of triglycerides: results from the Prospective Cardiovascular Münster (PROCAM) Study.

In the PROCAM study hypertriglyceridaemia was much more common among men (18.6%) than women (4.2%). Prevalence increased with age in women, but remained nearly constant at about 20% in men aged 35 years or more. In a multiple regression analysis a strong negative correlation between triglycerides and HDL cholesterol was found. A positive relationship was observed with cholesterol, blood glucose, factor VIIc, and PAI-1 in both sexes. Only in men, triglycerides are positively correlated with Apo A-I, body mass index, cigarette smoking, and alcohol consumption. Postmenopausal women showed higher triglyceride levels than premenopausal women. No independent relationships were observed to age, blood pressure, Lp(a), Apo A-II, Apo B, AT-III, protein C, fibrinogen, and oral contraceptives. A longitudinal analysis of data from 4474 male PROCAM participants aged 40-64 years with a follow-up of 4 years did not identify triglycerides as an independent risk factor, but the data suggest hypertriglyceridaemia is an additional risk factor for CHD, when excessive triglycerides coincide with a high ratio of plasma cholesterol to HDL-cholesterol and with low HDL-cholesterol values.

Adolescent↗

The effect of diazoxide-induced hormonal secretion on plasma triglyceride concentration in the rat.

The relationship between non-esterified fatty acid (NEFA) mobilization and hepatic conversion to plasma triglycerides (TG), as modulated by diazoxide-induced effects upon endogenous catecholamine, glucagon, and insulin secretion, was examined in vivo in the rat. Thyrotropin (TSH)-induced NEFA mobilization provided the control study.--In all control experiments, TSH (1.5 IU/100 g) induced a 110% increase in NEFA availability, which was associated with a subsequent 52% increase in plasma TG concentration and a 73% increase in plasma ketone bodies. Following diazoxide administration (30 mg/kg), endogenous secretion of both catecholamines and glucagon was observed, resulting in a comparable 100% increase in NEFA availability, with the appropriate ketonaemic response. However, in contrast to the control TSH study, plasma triglyceride concentration did not increase. This suppression was secondary, at least in part, to a direct 40% inhibition of hepatic secretion of triglycerides.--Although plasma NEFA concentration is an important determinant of plasma triglyceride levels, the concurrent concentration of endogenous catecholamines, glucagon, and insulin modulate the hepatic conversion of NEFA to triglycerides in vivo.

Animals↗

Muscle triglycerides in diabetic subjects. Effect of insulin deficiency and exercise.

Muscle triglycerides and glycogen were measured in biopsy specimens of the vastus lateralis muscle before and after 1 h of ergometric exercise at 50 to 60% of maximal capacity (i. e. at a pulse rate during exercise of 180 minus age) in 3 groups of 19 to 35 year old, non-obese male subjects: 10 normals, 10 insulin dependent diabetic patients in relatively good control and 10 poorly controlled insulin dependent diabetic patients in whom insulin was withdrawn 24 h prior to examination. At rest in all subjects muscle triglyceride content was positively correlated with serum triglycerides(p < 0.001) and blood glucose (p < 0.05), resulting in elevated muscle triglyceride stores in the insulin deficient diabetic patients (17.9 +/- 1.8 mumol/g protein vs. 13.4 +/- 1.3 and 9.4 +/- 1.2 in the normal subjects and the well controlled diabetic patients; p < 0.05 and < 0.001). During exercise, utilisation of muscle triglycerides and glycogen were directly related to content at rest (p < 0.001), including the insulin-deprived patients with decreased glycogen. The decrease of muscle fat was associated with a rise in serum glycerol (p < 0.001) and non-esterified fatty acids (p < 0.001) during exercise.

Adult↗

The effects of the alpha-glucosidase inhibitor BAY g 5421 (Acarbose) on postprandial blood glucose, serum insulin, and triglyceride levels: dose-time-response relationships in man.

In a double-blind quadruple cross-over study the effect of a new alpha-glucosidase inhibitor (BAY g 5421) on postprandial blood glucose, serum insulin, and serum triglyceride increases was tested in 24 male healthy volunteers. They received before a standardized breakfast 50, 100, or 200 mg of BAY g 5421 or a placebo per os. The dose-time-response relationships were calculated and the drug tolerance was assessed. There was a statistically significant inhibition of the postprandial increases of the blood glucose, serum insulin, and triglyceride values. Further analysis showed no dose-dependent effect of the drug on the blood glucose values, whereas the serum insulin and triglyceride values were affected in a dose-dependent fashion. The maximal inhibitory effect on the serum insulin levels occurred 69 min after breakfast and on the serum triglyceride levels 104 min after breakfast. One hundred and 200 mg of BAY g 5421 were equally inhibitory-effective on the serum insulin levels, whereas the highest dose used was markedly more effective on serum triglyceride values than lower doses. Based on these results, a dosage of 100--200 mg of BAY g 5421/meal is recommended for clinical trials in metabolic diseases.

Administration, Oral↗

Plasma triglyceride and beta-hydroxybutyric acid levels in red-sided garter snakes (Thamnophis sirtalis parietalis) at emergence from hibernation.

Measurement of plasma levels of triglycerides and beta-hydroxybutyric acid in females and males of the red-sided garter snake (Thamnophis sirtalis parietalis) suggest that the former may provide a useful physiological marker of condition. Levels of triglycerides at emergence from hibernation during a month of natural aphagia were significantly greater in females than in males and she-males, a subset of the male population that mimics females. Higher levels of triglycerides in the females may be attributed to their greater body mass per unit length, which was correlated with the level of triglycerides. Plasma triglyceride levels declined in females within one month of emergence, at the onset of feeding, and were unrelated to mating.

3-Hydroxybutyric Acid↗

Cardiopathogenicity of soybean oil and tower rapeseed oil triglycerides when fed to male rats.

The triglycerides of soybean oil were purified by molecular distillation and those of Tower rapeseed oil by molecular distillation and adsorption chromatography. The original oils and the purified triglycerides were incorporated in semisynthetic diets at 20% by weight and fed for 16 weeks to weanling male Sprague-Dawley rats to compare the nutritional and pathological effects of the oils and their triglyceride fractions on rats. The study was carried out at two independent laboratories. No significant differences were observed between the results of the two establishments. The incidence of myocardial lesions was significantly higher in rats fed Tower rapeseed oil than in those fed soybean oil. Purification of the triglycerides by molecular distillation and adsorption chromatography appeared to have no major effect on the incidence of myocardial lesions. This supports our previous findings that the cardiopathogenicity appeared to have no major effect on the incidence of myocardial lesions. This supports our previous findings that the cardiopathogenicity of the test oils to rats resides in the triglycerides of these oils.

Animals↗

The role of dietary fat and hepatic triglyceride secretion in cancer-induced hypertriglyceridemia.

Growth of Ehrlich ascites carcinoma induces hyperlipemia in mice. In the present study using male Swiss-Webster mice, we examined whether the usual elevations of plasma triglyceride levels in cancerous mice would occur in the absence of dietary fat. Hypertiglyceridemia developed at a similar rate and to a comparable degree in tumerous mice eating a fat-free (58% glucose) diet and in those fed Purina chow. Maximal hyperlipidemia was observed on day 6 or day 8 in tumorous mice fed either diet. To determine whether the endogenous cancer-induced hyperlipidemia was due to hypersecretion of triglycerides by the liver, triglyceride secretion rates were studied 0, 2, 4, 6, 8, 10, and 12 days after tumor inoculation using Triton WR-1339. The secretory rates did not increase prior to or during the development of hypertriglyceridemia in tumorous mice and were not significantly different from those of control mice. On days 10 and 12, triglyceride secretion actually decreased in tumorous mice. Other possible causes for hypertriglyceridemia are discussed in light of the present findings of undetectable differences in triglyceride secretion rates accompanying growth of Ehrlich ascites carcinoma in mice.

Animals↗

Fatty acid chain length combinations in ascitic fluid triglycerides containing lymphatic absorbed medium-chain fatty acids.

Information on the fatty acid chain length combinations in lymph triglycerides containing medium-chain fatty acids was obtained by combining the fatty acid composition and the carbon number composition of triglycerides from ascitic fluid of patients on medium-chain triglyceride-containing diets. In these triglycerides, the major part of the medium-chain fatty acids was present in combination with long-chain fatty acids. These results indicate that part of the lymphatic absorbed medium-chain fatty acids are absorbed as triglycerides which also contain long-chain fatty acids.

Ascites↗

Adipose hormone-sensitive lipase preferentially releases polyunsaturated fatty acids from triglycerides.

Rat adipose hormone-sensitive lipase-mediated release of fatty acids from triglycerides was studied in three model systems: i) cultured preadipocytes containing polyunsaturated fatty acid-enriched triglyceride; ii) perfused epididymal fat pads; and iii) in vitro incubations of crude preparations of hormone-sensitive lipase with synthetic triglyceride-analogues as substrates. We found that cultured preadipocytes challenged with 10 microM norepinephrine tended to release more omega 6 and omega 3 polyunsaturated fatty acids than saturated fatty acids. Fat pads perfused with 10 microM norepinephrine preferentially released arachidonate and alpha-linolenate but tended to retain oleate and linoleate. Finally, crude preparations of hormone-sensitive lipase released from the triglyceride-analogue substrates alpha-linolenate twice as fast as oleate. We conclude that rat adipose hormone-sensitive lipase preferentially releases polyunsaturated fatty acids from triglycerides. We suggest that this may be a mechanism by which these fatty acids are kept from being trapped in fat depots and maintained in the circulation.

Adipose Tissue↗

LCAT inhibitors interfere with the enzymatic determination of cholesterol and triglycerides.

5,5-Dithiobis-(2-nitrobenzoic acid) (DTNB) and p-chloro-mercuriphenylsulfonic acid (PCMPS) are well-known sulfhydryl inhibitors that are used to inhibit lecithin: cholesterol acyltransferase (LCAT). They were each found to interfere with the enzymatic assays of cholesterol and triglycerides. DTNB falsely reduced the measured plasma cholesterol content, and falsely increased triglyceride readings. The interference with the triglyceride assay could be largely prevented by blanking for glycerol. PCMPS had only a slight effect on the cholesterol assay, but falsely lowered the triglyceride readings to a great extent, even with glycerol-blanking. Thus, these inhibitors should be avoided when plasma samples are to be enzymatically analyzed for cholesterol or triglycerides.

4-Chloromercuribenzenesulfonate↗

Changes in sodium-lithium countertransport correlate with changes in triglyceride levels and body mass index over 2 1/2 years of follow-up in Utah.

We have previously reported from a cross-sectional study that plasma total cholesterol, triglycerides, and HDL-C were significantly and independently correlated with Na(+)-Li+ countertransport. These original participants were rescreened 2 1/2 years later (range of 20-58 months), with lipid, blood pressure, and Na(+)-Li+ countertransport measurements from both visits on 906 normotensive adults. The correlation found between age- and sex-adjusted triglyceride levels and Na(+)-Li+ countertransport at visit 1 (r = 0.34, p less than 0.0001) was reconfirmed at visit 2 (r = 0.32, p less than 0.0001). The Na(+)-Li+ countertransport correlations with HDL-C (r = -0.11, p less than 0.01) and body mass index (r = 0.24, p less than 0.0001) also remained at visit 2. After 30 months, there were significant increases of triglyceride, body mass index, blood pressure, and Na(+)-Li+ countertransport levels, and significant decreases of HDL-C and total cholesterol levels, after adjusting the changes in these variables between visit 2 and visit 1 for age, sex, time between the two visits, and the visit 1 level of the variable. Increases in triglycerides, cholesterol, and body mass index were significantly correlated with increases in Na(+)-Li+ countertransport (r = 0.23, r = 0.19, and r = 0.21, respectively). The correlations of the lipid and lipoprotein changes with Na(+)-Li+ countertransport changes were independent of body mass index and blood pressure changes. We conclude that increasing plasma triglyceride levels and body mass index are associated with increasing Na(+)-Li+ countertransport levels in both cross-sectional and longitudinal data.

Adolescent↗

Production of butyrylcholinesterase by Caco-2 cells: lack of relationship with triglyceride production.

Elevated levels of butyrylcholinesterase activity occur under a number of hypertriglyceridemic conditions, including diabetes and obesity. This study examines whether butyrylcholinesterase activity has a direct effect on triglyceride production, using Caco-2 cells, a human intestinal adenocarcinoma cell line. Caco-2 cells were incubated with 500 microM oleate to stimulate triglyceride production, and butyrylcholinesterase activity was measured in the cellular homogenate. Butyrylcholinesterase activity was approximately 3 x 10(-3) micromol/min per milligram protein. Although triglyceride production increased by almost five-fold after 18 h of stimulation with oleate, butyrylcholinesterase activity was not increased. Furthermore, inhibition of butyrylcholinesterase activity using 1 mM tetraisopropylpyrophosphoramide did not significantly affect triglyceride production or secretion. Human insulin (100 microU/ml) increased the production of butyrylcholinesterase without increasing triglyceride production. This demonstrates that stimulation of fatty acid production and butyrylcholinesterase activity occur by independent mechanisms and suggests that their correlation in hyperlipidemic conditions is not due to a direct relationship in production in situ.

Butyrylcholinesterase↗

The apolipoprotein A-V genotype and plasma apolipoprotein A-V and triglyceride levels: prospective risk of type 2 diabetes. Results from the Northwick Park Heart Study II.

AIMS/HYPOTHESIS: We sought to establish the relationship between plasma apolipoprotein A-V (APOA5, previously known as apoA-V) and triglyceride levels and to determine the impact of the APOA5 genotype on APOA5 levels and development of type 2 diabetes in a 15-year follow-up study of healthy UK men. MATERIALS AND METHODS: APOA5 -1131T>C and S19W genotypes were determined in 2,490 men, of whom 145 subsequently developed type 2 diabetes. In a subset of 299 men, we also determined APOA5 levels. RESULTS: Plasma APOA5 levels positively correlated with triglycerides (r=0.18, p<0.002) and were not different in men who subsequently developed type 2 diabetes compared with healthy men (p=0.7). Carriers of either APOA5 W19 or -1131C had, as expected, higher plasma triglycerides. However, while W19 carriers had significantly higher APOA5 levels (p=0.0003), APOA5 levels were not associated with -1131T>C (p=0.63), reinforcing the idea that the reported -1131C association with triglycerides levels is due to linkage disequilibrium with variants in the APOC3 gene, and not due to the direct effect on APOA5 levels. Overall no effect of APOA5 -1131T>C or S19W was found on type 2 diabetes risk. CONCLUSIONS/INTERPRETATION: In contrast to animal studies, in man, plasma APOA5 positively correlates with plasma triglyceride levels. In prospective analysis, with the caveat that numbers were small, APOA5 genotypes do not appear to have an impact on risk of development of type 2 diabetes.

Apolipoprotein A-V↗

Noradrenaline and ATP decrease the secretion of triglyceride and apoprotein B from perfused rat liver.

To explore the role of hepatic sympathetic nerves on the secretion of very low density lipoprotein (VLDL), the effects of sympathetic neurotransmitters, noradrenaline and ATP, on the secretion of triglyceride and apoprotein B (ApoB) from the liver were studied using rat liver perfused in situ with recirculation. During liver perfusion with physiological medium, the amount of triglyceride in the perfusate was increased linearly for up to 120 min. The addition of noradrenaline to the perfusion medium at a final concentration of 1 muM increased the portal pressure and suppressed the secretion of triglyceride to about 60% of control without an increase in free fatty acid production. The administration of ATP increased the portal pressure with kinetics different from those induced by noradrenaline, but suppressed the triglyceride secretion to an extent similar to that induced by noradrenaline. The suppressive effect of noradrenaline on triglyceride secretion was mimicked by an alpha-adrenoceptor agonist, phenylephrine, and was retained after the haemodynamic changes were prevented by sodium nitroprusside. The secretion of ApoB from the perfused liver was also inhibited by noradrenaline or ATP to about 70% of control. However, hepatic levels of mRNA for ApoB were not significantly altered by noradrenaline and ATP. Since ApoB is the major apoprotein in VLDL, these results suggest that the sympathetic neurotransmitters noradrenaline and ATP suppress the secretion of ApoB-containing lipoprotein including VLDL from the liver, probably acting on post-transcriptional processes.

Adenosine Triphosphate↗

Isostatic ultra-high-pressure effects on supercooled melts in colloidal triglyceride dispersions.

PURPOSE: Colloidal triglyceride dispersions can form metastable supercooled melts that need tedious tempering processes to be transformed into a crystalline state. We investigated the possibility of transforming the supercooled melts into crystals in a short time by treatment with isostatic high pressure. METHODS: Nanosized supercooled melts of triglycerides in aqueous dispersions (prepared by high-pressure homogenization) were exposed to isostatic ultrahigh pressure for short periods to initialize crystallization processes. The dispersions were analyzed with different appropriate measuring methods such as differential scanning calorimetry, nuclear magnetic resonance, X-ray scattering, and electron paramagnetic resonance. The resulting particle sizes were estimated by photon correlation spectroscopy and transmission electron microscopy. RESULTS: The results of differential scanning calorimetry, X-ray, and nuclear magnetic resonance experiments show the induction of triglyceride particle crystallization by high-pressure treatment. Electron paramagnetic resonance spectroscopy shows that the triglyceride crystallization coincides with relocation of the lipophilic probe into a more polar environment. Transmission electron microscopy micrographs show the transformation of supercooled liquid particles into crystallized anisotropic particles. CONCLUSION: Crystal transformation in nanoscaled systems can be delayed for months, depending on the materials and the composite. It is shown that isostatic high-pressure treatment can be a valuable method to induce, accelerate, and control crystallization processes in specific colloidal triglyceride dispersions.

Cold Temperature↗

Effect of liposome-encapsulated hemoglobin on triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol measurements.

The present study investigated the effect of liposome-encapsulated hemoglobin (LEH), an experimental oxygen-carrying resuscitation fluid, on triglyceride, total cholesterol, and low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol measurements. In vivo, the intravenous infusion of LEH (5.6 mL/kg, n = 6) elevated serum triglycerides (+92% vs. baseline, P < .05), total cholesterol (+25% vs. baseline, P < .01), LDL cholesterol (+72% vs. baseline, P < .01) and had no effect on serum HDL cholesterol. In addition, LEH did not alter the elevation in serum triglycerides (+302% vs. baseline, P < .01) and LDL cholesterol (+86% vs. baseline, P < .01) induced by lipopolysaccharide (3.6 mg/kg, i.v., n = 6. Ex vivo, measurements of triglycerides and total cholesterol as well as LDL and HDL cholesterol in whole blood from naive rats were not changed by the addition of LEH (0-50%, n = 6). In vitro, the addition of a fixed concentration of LEH (50%, n = 6) to varying concentrations of cholesterol solution (0-50%), or vice versa, had no effect on cholesterol determination. It is therefore concluded that LEH only minimally affects serum levels of triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol and does not interfere with their measurement.

Animals↗