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PubMed2000

Efficacy and tolerability of fluvastatin and bezafibrate in patients with hyperlipidemia and persistently high triglyceride levels.

Hyperlipidemia is an important cardiovascular risk factor. Lipid-lowering therapy has been shown to decrease morbidity and mortality in these patients. Combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and a fibric-acid derivative has been reported to be more efficacious to reduce low-density lipoprotein (LDL) cholesterol and triglycerides but may be associated with an increased risk of myositis. The aim of this study was to investigate the efficacy and tolerability of fluvastatin, an HMG-CoA reductase inhibitor, alone and in combination with bezafibrate, a fibric-acid derivative. In a randomized controlled trial with 454 hypercholesterolemic patients (mean cholesterol, 8.6 +/- 1.6 mM), fluvastatin (20 mg/day) significantly lowered total plasma cholesterol levels (-12.5%; p < 0.0001 vs. placebo), LDL cholesterol (-14%; p < 0.0001), and triglycerides (-4%; p = 0.05). A small increase in high-density lipoprotein (HDL) cholesterol levels (3%, NS) also was observed. Combination therapy with fluvastatin and bezafibrate (400 mg/day) in 71 patients with persistent hypertriglyceridemia during treatment with the statin resulted in a more pronounced reduction in triglyceride (-47%; p < 0.0001) and total cholesterol levels (-15%; p < 0.0001) than did fluvastatin alone. Furthermore, the additional bezafibrate significantly increased HDL cholesterol (+5%; p < 0.001). No significant increases in creatine phosphokinase levels or in frequency of myalgia were observed. In summary, fluvastatin decreases both cholesterol and triglyceride levels. In patients with persistent hypertriglyceridemia, combination therapy with fluvastatin and bezafibrate may be safely used to lower triglyceride and cholesterol levels more efficiently.

Adult↗
PubMed1976

Involvement of phospholipids in triglyceride biosynthesis by developing soybean cotyledons.

The incorporation of phospholipids specifically labeled with glycerol-2(3)H and acyl-(14)C by whole cell tissues of developing soybean cotyledons (Glycine max L.) reveals that phosphatidylinositol, phosphatidylcholine, phosphatidylethanolamine, N-acylphosphatidylethanolamine, and phosphatidic acid can be metabolized to diglyceride. The diglyceride formed may be recylced into phospholipid or acylated to triglyceride. Diglyceride from phosphatidic acid and phosphatidylethanolamine is used readily in triglyceride biosynthesis compared to the other phospholipids. Incorporation of N-acylphosphatidylethanolamine having [9-10-(3)H(N)]oleic acid esterified at sn-3 in cotyledons shows rapid acyltransfer of (3)H into triglyceride and therefore N-acylphosphatidylethanolamine appears to participate in triglyceride biosynthesis as an acyl donor. These studies emphasize phospholipid metabolism in developing soybean cotyledons is a dynamic process which plays a key role in triglyceride formation.

Journal Article↗
PubMed1982

Maximal lymphatic triglyceride transport rate from the rat small intestine.

In previous studies, we demonstrated that the hydrophobic surfactant Pluronic L-81 blocks lymphatic triglyceride transport from the small intestine and leads to accumulation of triglyceride in the mucosa. The onset of action of Pluronic L-81 is rapid and quickly reversed once its administration is discontinued. We have taken advantage of these effects of Pluronic L-81 on intestinal lipid transport in order to determine the apparent maximal triglyceride transport capacity of the proximal half of the rat small bowel using lymph fistula rats infused intraduodenally with a phosphate-buffered, taurocholate-stabilized emulsion containing 40 mumol [3H]triolein and 0.5 mg Pluronic L-81 at 3 ml/h for 8 h to load the proximal small bowel with lipid. Studies were done in one group of rats in order to be certain that only the proximal half of the small bowel contained 3H-lipid after this period of infusion. In other rats treated similarly, the 8 h of lipid-Pluronic L-81 infusion were followed by infusion of 3 ml/h of 0.15 M salt solution for 5 h. Lymphatic transport of lipid was determined throughout the entire period of infusion. During lipid-Pluronic L-81 infusion, transport of 3H-triglyceride fatty acid into lymph was only 22-27 mumol/h but rose steadily after substitution of saline and reached a maximal transport rate of 109 +/- 6.2 mumol/h (means +/- SE) after 3.5 h. During this 3.5-h period, the amount of 3H-lipid in the proximal mucosa declined from 530 to 263 mumol. While Pluronic L-81 was infused, only very low-density-lipoprotein-sized particles were seen in lymph by electron microscopy, whereas, at the peak of triglyceride transport during saline infusion, chylomicrons of up to 6,000 A were observed in lymph.

Animals↗
PubMedDate not supplied

[The effect of fatty emulsions with distinct triglyceride compositions on the lipid metabolism of the septic patient].

OBJECTIVE: To assess the effects on the intravascular lipid mechanism of fatty emulsions with an identical lipid concentration and a different triglyceride composition administered as part of the total parenteral nutrition (TPN) in septicemic patients hospitalized in the intensive care unit (ICU). One emulsion will be made up of long chain triglycerides, LCT (20% Intralipid) (group I) and the other will be made up by a mixture of medium- and long-chain triglycerides, MCT/LCT (1:1) (20% Lipofundina) (group II). AREA: Vall d'Hebrón General University Hospital. Intensive care unit, Biochemistry laboratory, nutritional support unit, and Department of Pharmacy. PATIENTS: 12 septicemic patients who required TPN were studied, and these patients were randomly given one of the two lipid emulsions for a five day period. Prior to initiating the TPN and before ending it, blood samples were drawn for the analysis of the lipoprotein components VLDL, LDL, and HDL isolated by ultracentrifugation, and the basic lipid and nutritional parameters. RESULTS: The baseline statistical analysis shows that even though both groups are not comparable, the composition of the VLDL, LDL, and HDL lipoproteins differs from the reference values. After five days of TPN, the metabolic behavior of the groups is different, in group I the concentrations of reactive C protein (RCP) decreased as did the HDL phospholipids, while group II presented an increase in the plasma triglyceride levels, the VLDL cholesterol, the LDL triglycerides, and the HDL proteins. CONCLUSIONS: Septicemic patients present in altered lipoprotein pattern that tends to normalize after 5 days of lipid emulsions administration.

Adult↗
PubMed1990

Protein disulfide isomerase is a component of the microsomal triglyceride transfer protein complex.

A bovine liver protein which catalyzes the transfer of triglyceride between membranes has previously been isolated from the lumen of the microsomal fraction. When further purified about 100-fold, two polypeptides of molecular mass 58,000 and 88,000 were identified (Wetterau, J. R., and Zilversmit, D. B. (1985) Chem. Phys. Lipids 38, 205-222). We demonstrate here that the two polypeptides (referred to as 58-kDa and 88-kDa, respectively) are associated in a protein-protein complex, and that the triglyceride transfer activity is associated with this complex. Antibodies specific for either polypeptide immunoprecipitated both the 58-kDa and 88-kDa polypeptides as well as the lipid transfer activity. The 58-kDa subunit of the microsomal transfer protein complex was identified as protein disulfide-isomerase (PDI) (EC 5.3.4.1) by 1) a comparison of the amino-terminal sequence of PDI and the 58-kDa subunit of the transfer protein, 2) a comparison of the reverse phase high performance liquid chromatography peptide maps of CNBr digests of PDI and the lipid transfer protein, 3) immunoprecipitation competition experiments in which PDI was found to compete with the lipid transfer protein for immunoprecipitation by the anti-58-kDa polyclonal antibodies, 4) immunological cross-reactivity of the microsomal triglyceride transfer protein complex with polyclonal antibodies raised against PDI, and 5) the appearance of protein disulfide isomerase activity following the dissociation of purified microsomal transfer protein complex with guanidine HCl. In conclusion, the microsomal triglyceride transfer protein has a multi-subunit structure which is unique compared to other intracellular lipid transfer proteins which have been described to be single polypeptides. The unexpected finding that PDI is a component of the microsomal triglyceride transfer protein complex suggests a new previously undescribed role for protein disulfide isomerase.

Amino Acid Sequence↗
PubMed1966

Temperature independence of the composition of triglyceride fatty acids synthesized de novo by the mosquito.

The hypothesis that depot fat is more unsaturated when it is synthesized at lower temperatures was tested in the mosquito. Female mosquitoes (Aedes sollicitans) were starved until no triglycerides remained. A single dose of sugar was fed and the mosquitoes were maintained at different temperatures. Approximately the same amount of triglyceride was synthesized per mosquito at each temperature, although at different rates. Mosquitoes maintained at low temperatures did not synthesize more unsaturated triglycerides than those at higher temperatures: the fatty acid composition was essentially the same from 10 to 35 degrees. The triglycerides synthesized from sugar contained no poly-unsaturated fatty acids. Total amounts and composition of phospholipid fatty acids remained unaltered during sugar feeding. When deprived of food, the mosquitoes catabolized triglyceride fatty acids randomly; cold-exposure did not cause selective retention or utilization of any individual fatty acid.

Adipose Tissue↗
PubMed1978

Release of phospholipase A and triglyceride lipase from rat liver.

A new, rapid, and sensitive assay for phospholipase A, utilizing commercially available [14C]phosphatidylethanolamine with 14C label in both palmitic acid moieties, was used to study phospholipase A release from perfused liver, hepatocytes, and intestinal cells from rats. Heparin triggered a prompt release of phospholipase A from perfused liver. Phospholipase A and triglyceride lipase were released from hepatocytes at a linear rate for 1 h and 30 min, respectively. Heparin (20 u/ml) doubled the release of phospholipase A and triglyceride lipase from hepatocytes. Colchicine (0.1 mM), but not puromycin (0.2 mM), inhibited basal and heparin-stimulated phospholipase A release by 40%. Since the amount of phospholipase A and triglyceride lipase released into the medium greatly exceeded intracellular activities, it is possible that secretion is coupled with intracellular conversion from inactive to active forms of the enzymes. Dibutyryl cyclic AMP (1 mM) inhibited phospholipase A (48%) and triglyceride lipase (82%) release from hepatocytes. Epinephrine, dexamethasone, and clofibrate inhibited release of triglyceride lipase but not phospholipase A. Phospholipase A activity of intestinal cells was greater than in hepatocytes, but neither heparin nor dibutyryl cyclic AMP affected phospholipase A release from intestinal cells. These results suggest that the liver is a major source of phospholipase A of postheparin plasma. The fact that dibutyryl cyclic AMP affects the release of these enzymes suggests an additional mechanism for hormonal regulation of lipid and lipoprotein metabolism.

Animals↗
PubMed1981

[Familial Mediterranean fever and fatty liver. effect of a long time colchicine treatment on triglyceride storage (author's transl)].

A 35-year-old man, sephardic jew, complains for the last eleven years of typical and frequent attacks of FMF. His liver is hypertrophic. Needle-biopsy reveals an extensive macrovacuolar triglyceride storage (60 per cent) and an active vascular congestion with erythrodiapedesis in the mild and centrolobular zone, without any necrosis, cellular infiltration nor fibrosis. Electron microscopy shows lipofuschin deposits and mild lesions of mitochondrias, endoplasmic reticulum. Blood triglycerides and apo B are rather low. After six weeks of colchicine treatment, needle biopsy shows no more active congestion nor erythrodiapedesis. Triglyceride storage lowers to 40 per cent. After seven months of colchicine treatment, triglyceride storage falls down to 12 per cent. FMF may be considered as a cause of fatty liver when there is not any cause else and only after deep decrease or disparition of triglyceride deposit by a long time colchicine treatment.

Adult↗
PubMed1995

Lipid profile in women with preeclampsia: relationship between plasma triglyceride levels and severity of preeclampsia.

It has been hypothesized that, in preeclampsia, hypertriglyceridemia may lead to increased endothelial triglyceride accumulation that, in turn, may result in endothelial cell damage. The purpose of our study was to determine whether hypertriglyceridemia is associated with the severity of preeclampsia. We studied 29 preeclamptic patients and 46 normal pregnant women, aged 15 to 35 years, with singleton pregnancies, at 28 to 37 weeks' gestation. Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were measured enzymatically. High-density lipoprotein cholesterol was determined using a dextran sulfate-magnesium precipitation method. Patients with mild preeclampsia had a significant increase in plasma triglyceride levels (P < .001), while patients with severe preeclampsia had triglyceride levels comparable to controls. Our findings suggest that there is no direct relationship between triglyceride levels and severity of preeclampsia.

Adolescent↗
PubMed1981

Serum cholesterol and triglyceride levels in school-age population. Distribution, correlation, and prevalence of high values.

The distribution of serum cholesterol and triglycerides, the prevalence of high values, and their correlations with other variables were studied in a sample of the school population of Caracas, Venezuela, 6 to 15 years of age (1,385 boys and 1,412 girls). The mean serum cholesterol level was 156.36 mg/dL in girls and 153.10 mg/dL in boys, remaining stable during the whole age range in both sexes. Mean serum triglyceride level was significantly higher in girls than in boys. In girls, mean serum triglyceride level increased uniformly with age between ages 6 and 15 years, whereas in boys it remained stable after age 9 years. Serum cholesterol levels above 160 mg/dL were observed in 43.9% of the girls and in 38.2% of the boys. Our findings suggest that the association of serum cholesterol and triglyceride levels with weight mainly reflects the adipose tissue component of body weight.

Adolescent↗
PubMed2001

Which fasting triglyceride levels best reflect coronary risk? Evidence from the Turkish Adult Risk Factor Study.

BACKGROUND: Association between raised low-density lipoprotein cholesterol (LDL-C) levels and high risk for coronary heart disease (CHD) is well established and taken into account in guidelines on coronary prevention. HYPOTHESIS: The relationship between risk for coronary heart disease (CHD) and the levels of fasting plasma triglycerides was studied in the cohort of the Turkish Adult Risk Factor Study, a representative random sample of an adult population. METHODS: In 829 men and 907 women aged > or =27 years (mean 48.5+/-11), plasma lipids and lipoproteins were measured by the enzymatic dry method in the postabsorptive state. A sample of values was validated in a reference laboratory. Apoliprotein (apo) A-I and B were measured by the turbidimetric immunoassay using commercial kits in part of the cohort. Blood pressure and anthropometric measurements were made. Criteria for the diagnosis of CHD were based on history, cardiovascular examination, and Minnesota coding of resting electrocardiograms. Coronary heart disease was diagnosed in about 7% of the subjects. Participants were divided into four categories depending on their triglyceride levels: I = < 100 mg/dl (282 men, 400 women), II = 100-139 mg/dl (204 men, 228 women), III = 140-212 mg/dl (188 men, 180 women), and IV = > or = 212 mg/dl (155 men, 99 women). RESULTS: After adjustment for age, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, smoking, and body mass index by logistic regression analysis, and after assigning the CHD risk of 1 to Category I, the relative risk for men and women combined rose to 1.42 in Category III (p<0.045) while it diminished to 0.94 in Category IV (p = 0.79). In women, the odds ratio (OR) rose gradually up to 1.78 (p< 0.025) in Category III, only to decline in Category IV. The OR in men was slightly, insignificantly, and equally elevated in Categories III and IV. Patients with CHD in Category III were not distinguished from those in Category IV by the studied risk parameters. It was suggested that high risk for CHD--particularly in subjects with slightly elevated or normal cholesterol levels-is often not reflected by extreme increases of fasting triglycerides but best by modest elevations (140-212 mg/dl), which serve better as a marker of triglyceride-rich lipoprotein particles. This knowledge may prove to be of value in population screening and individual risk assessment.

Adult↗
PubMed1982

[Effect of long-time supply of medium-chain triglycerides on postprandial lipid metabolism and fatty acid pattern of membrane lipids in rats].

To characterize the effect of long-term supply medium-chain triglycerides on the lipid metabolism, the authors determined under postprandial conditions the ratio between the ketone body concentrations in the blood and the liver, the in vitro fatty-acid synthesis in the liver and the adipose tissue, the plasma and liver lipids and the fatty-acid and phospholipid spectra of the plasma and the erythrocytic, thrombocytic and liver mitochondrial membranes, in rats after 9 weeks on an isoenergetic diet containing 12% of medium-chain triglycerides or lard. The long-term supply of medium-chain triglycerides induced a 3-fold increase of the fatty-acid synthesis in the liver and the fatty tissue. In contrast to this, no differences in the concentrations of acetacetate and beta-hydroxybutyrate were detected in the liver and the adipose tissue. The triglyceride and cholesterol contents in the liver were significantly reduced. In spite of the increase of palmitic acid proportion as the end product of the de novo fatty-acid synthesis in the plasma lipids and the erythrocytic membrane, the proportion of essential fatty acids in the membrane lipids under study was not affected; the simultaneous supply of 3% of sunflower oil meets the requirements for essential fatty acids.

Adipose Tissue↗
PubMed2004

Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats.

Dietary fatty acid composition modifies hepatic lipid metabolism. To determine the effects of fatty acids on hepatic triglyceride storage, rats were fed diets enriched in carbohydrates (control), fish oil, or lard. After 4 weeks, the animals were fasted overnight. In the morning, the animals were either sacrificed or fed 8 g of their respective diets before sacrifice. Animals ingested more food calories with diets containing fish oil than with other diets. However, fish oil-fed animals weighed less and had less body fat. In fish oil-fed animals, liver triglyceride was lower by 27% (P <.05) and 73% (P <.01) than in control- and lard-fed animals, respectively. Fish oil altered the postprandial gene expression of hepatic regulators of fatty acid degradation and synthesis. Fish oil feeding blunted the normal postprandial decline in fatty acid degradation genes (PPARalpha, CPT1, and ACO) and blunted the normal postprandial rise in triglyceride synthesis genes (SREBP1-c, FAS, SCD-1). Therefore, the direct postprandial effect of fish oil ingestion decreases the propensity for hepatic triglyceride storage. In conclusion, n-3 polyunsaturated fatty acids decrease total body weight, total body fat, and hepatic steatosis.

Animals↗
PubMed1996

Noninvasive assessment of hepatic triglyceride content in humans with 13C nuclear magnetic resonance spectroscopy.

Hepatic lipid content was assessed noninvasively in 15 patients with hepatic steatosis by 13C nuclear magnetic resonance (NMR) spectroscopy, and compared in a double-blind fashion with histological grading and morphometric quantitation of fat in liver biopsies taken within 2 weeks of the study. The lipid content in the liver biopsies was expressed as the volume fraction of total parenchyma occupied by fat. Hepatic triglyceride content was determined by comparing the 13C NMR signal intensity in vivo with the signal intensity obtained from a lipid phantom of known concentrations. There was an approximately 30-fold increase in the 13C NMR signals of the saturated carbons (methyl/methylene [CH2]n) region of hepatic triglycerides from patients with grade 4 steatosis compared with those with grade 0, yielding a good dynamic range for measuring hepatic triglyceride content. The correlation coefficient between the morphometric and 13C NMR techniques was 0.89 (P < .01). These studies demonstrate that 13C NMR spectroscopy can be used to noninvasively assess hepatic triglyceride content in humans. This method may be clinically useful for diagnosis and follow-up of patients with hepatic steatosis.

Adult↗
PubMedDate not supplied

Serum levels of albumin, triglycerides, total protein and glucose in rats are altered after oral treatment with low doses of 13-cis-retinoic acid or all-trans-retinoic acid.

Currently used to treat severe acne, 13-cis-retinoic acid (13-cis-RA) is under investigation for its anticancer effects as is the isomer, all-trans-retinoic acid (all-trans-RA). Here, the effects of oral 13-cis-RA or all-trans-RA treatment on serum chemistry, leptin and adiponectin levels were evaluated. Adult Sprague-Dawley rats were gavaged once daily for 7 consecutive days with 13-cis-RA (7.5 or 15 mg kg(-1)), all-trans-RA (10 or 15 mg kg(-1)) (n=24/sex/dose), or soy oil (n=16/sex) and blood was sampled 30-480 min after the last gavage. The body weight was unaffected; however, the liver/body weight ratios were increased by both doses of all-trans-RA. Sex differences were noted for levels of cholesterol, creatine, triglycerides, albumin, alanine aminotransferase and total protein. Both doses of all-trans-RA reduced albumin levels to approximately 90% of the control and total protein levels to approximately 93% of the control while substantially elevating triglyceride levels to approximately 66%-99% above the control. Additionally, triglyceride levels of the 15 mg kg(-1) 13-cis RA group were approximately 62% higher than the controls and total protein levels were approximately 5% less. Glucose levels were affected by sex and RA treatment in that males treated with 15 mg kg(-1) of 13-cis-RA or 10 mg kg(-1) all-trans-RA had lower (13%-19%) levels than the same-sex controls; however, females were not similarly affected. Neither 13-cis-RA nor all-trans-RA treatment had significant effects on the levels of blood urea nitrogen, aspartate amino transferase, leptin or adiponectin. On a mg kg(-1) basis, all-trans-RA was more potent than 13-cis-RA. These results replicate previous findings of RA-induced increased triglyceride levels. Additionally, several new findings indicate there may be sex-specific effects of RA treatment. Finally, neither treatment appeared to alter the typical diurnal cycles of these endpoints.

Administration, Oral↗
PubMed1998

Dietary taurine supplementation reduces plasma and liver cholesterol and triglyceride levels in rats fed a high-cholesterol or a cholesterol-free diet.

The effects of dietary taurine supplementation on plasma and hepatic lipid levels and phospholipid profiles were evaluated in rats fed a high-cholesterol or a cholesterol-free diet. Four groups of male rats were fed one of the following diets for 5 weeks: cholesterol-free diet (CFD); high cholesterol diet (HCD); high cholesterol, high taurine diet (HCHTD); or high taurine diet (HTD). Rats fed a HCHTD had significantly lower plasma levels of total cholesterol (32% reduction), LDL-cholesterol (37% reduction) and triglyceride (43% reduction) than rats fed a HCD alone. Plasma concentrations of total cholesterol, LDL-cholesterol and triglyceride were also significantly reduced in rats fed a HTD compared to rats fed a CFD. Taurine supplementation to the HCD significantly reduced hepatic cholesterol (50% decrease) and triglyceride (30% decrease) levels in rats. Taurine supplementation to the CFD also significantly reduced the hepatic triglyceride concentration (43% decrease) and elevated hepatic free fatty acid levels (77% increase) compared to rats fed only a CFD. These results suggest that dietary taurine supplementation is both hypocholesterolemic and hypotriglyceridemic in rats whose body cholesterol status is high or normal.

Animals↗
PubMed1975

Ultrastructure of the milk fat globule membrane with and without triglyceride.

The primary milk fat globule membrane (MFGM) around freshly secreted milk fat globules consists of a unit membrane separated from the triglyceride core by a dense material. This dense material may widen to include cytoplasmic organelles or may form small blebs. Preincubation and fixation of the globules at temperatures between 4 degrees C and 60 degrees C has no effect on the width or appearance of the dense material. Isolated MFGM profiles show structures identical to those found on intact globules. The dense material on the isolated MFGM profiles is unaffected by extractions which remove essentially all the triglyceride present in the pellets of MFGM. The structure of the primary MFGM is therefore independent of any triglyceride content and the earlier suggestions that the dark material represented a triglyceride layer of high melting point adsorped during cooling of the globules after milking are not supported by the work described in this paper.

Animals↗
PubMed1988

Increased serum concentrations of cholesterol and triglycerides in the progression of breast cancer.

The course of serum concentrations of cholesterol and triglycerides was investigated in patients with advanced breast cancer. The patients studied were divided into two groups according to their clinical status: group-I consisted of 51 patients who already had metastases at the start of the investigation, but progressed further during the time of observation; group-II consisted of 14 patients in remission who experienced recurrence of disease while under observation. In group-I, 28 patients (54.9%) were found to have normal serum triglyceride levels at the beginning of the observation period; 22 patients (78.6%) from this group experienced a significant (P less than 0.0001) increase above the normal range upon further disease progression. Similarly, serum cholesterol levels were normal in 32 patients (62.8%) at the start of the investigation, but increased significantly (P less than 0.0001) above the normal range upon disease progression. In group-II, 8 patients (57.2%) had normal serum triglyceride levels at the beginning of the observation period, but the levels increased in 4 patients (50%) significantly (P less than 0.005) upon the occurrence of metastases. Within the same group, a significant increase (P less than 0.001) of initially normal serum cholesterol levels was found in 4 (44.9%) out of 9 patients. In summary, a rise in serum levels of triglycerides and/or cholesterol should receive increased attention and could indicate progression or recurrence of breast cancer.

Aged↗