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Effect of a dietary supplement combination on weight management, adipose tissue, cholesterol and triglycerides in obese subjects.

A combination dietary supplement containing vitamins, minerals, herbs, fibers and amino acids was studied to determine its safety and efficacy on weight/ fat loss, cholesterol and triglycerides in a double-blind, placebo-controlled trail. Total body weight, body fat %, waist and hip measurements, total cholesterol and triglycerides were evaluated before and after 6 weeks treatment with combination supplement or placebo. The study population consisted in 27 mildly to moderately obese, otherwise healthy, volunteers. After 6 weeks of treatment, the combination supplement had a statistically significant (p<0.001, mu=0.05) positive weight reducing effect (-8.59Lb vs. +2.14 Lb). This weight reduction was associated with a corresponding statistically significant (p<0.001, mu=0.05) decrease in body fat % in the treatment group (-2.88%) vs. the placebo (+0.86%). In addition, significant decreases in total cholesterol (-22.94 mg/dL) and triglycerides (-39.29 mg/dL) were obtained plus reductions in waist and hip measurements. These positive results lead us to conclude, that the combination supplement studied herein is a safe and effective way to assist in weight/fat reduction and decreases in total cholesterol and triglycerides in relatively short time (6 weeks).

Adipose Tissue↗

Effect of a dietary supplement combination on weight management, adipose tissue, cholesterol and triglycerides in obese children.

A dietary supplement combination consisting of vitamins, minerals and fibers was studied to determine its safety and efficacy on weight/fat loss, cholesterol and triglycerides in children between ages 7-13. This open label trial measured total body weight, body fat percentage, waist circumference, total cholesterol, triglycerides before and after 6 weeks of treatment. The study population consisted of 25 mildly to moderate obese, otherwise healthy children of both sexes. After 6 weeks of treatment, the combination supplement had a statistically significant (p < 0.05) weight reducing effect. This weight reduction was associated with a corresponding statistically significant (p < 0.0001l) decrease in body fat percentage. In addition, significant decreases in total cholesterol (p < 0.0001) and triglycerides (p < 0.0001) were obtained, plus reductions in waist measurements. We conclude that the combination supplement studied herein is a safe and effective way to assist children in weight, fat percentage, cholesterol and triglyceride reduction.

Adipose Tissue↗

The effect of structured triglycerides on the kinetic stability of total nutrient admixtures.

PURPOSE: The physical stability of two types of total parenteral nutrient (TPN) admixtures was studied as a function of storage time and temperature. One of them contained only structured triglycerides and the other exclusively long-chain triglycerides as lipid components. METHODS: Droplet size of the mixtures was followed by photon correlation spectroscopy for 10 days. Zeta potential and dynamic surface tension measurements were carried out to evaluate the possible changes in the charge and interfacial surface tension of the emulsion droplets during the storage. pH values were monitored in order to follow the possible decomposition processes in the course of storage. RESULTS: Droplet size of emulsions prepared with lipids containing exclusively long-chain triglycerides showed remarkable increase after 4 days of storage in contrast with that of the mixtures containing structured lipids. CONCLUSIONS: The obtained results indicate that besides the advantageous metabolic effects of structured triglycerides, their application is recommended to improve the physical stability of TPN admixtures.

Drug Stability↗

Triglyceride in plasma: prospective effects on microcirculatory functions.

The effect of triglyceride in plasma on RBC aggregation was examined, and the prospective influence on the flow of RBCs in microcirculation and the O2 release was discussed. To minimize the individual differences, blood samples were collected from one subject 2 hrs after high-fat and low fat meals. Triglyceride content in plasma was measured by an enzymatic method, and the rate of rouleaux formation was measured with a low shear rheoscope. The rate of rouleaux formation was increased with the increase of triglyceride concentration. Our previous findings suggested some functional impairment in microcirculation. (1) The enhanced RBC aggregation tends to reduce flow resistance in arterioles, but results in inhomogeneous flow of RBCs in capillaries. (2) The sclerotic change of microvessels alters flow behavior of RBCs, and thereby flow resistance is increased. (3) The enhanced RBC aggregation reduces O2 release from RBCs flowing in microvessels. In conclusion, high triglyceride level in plasma not only changes flow behavior of RBCs in microcirculation and thus increases flow resistance, but also prevents homogeneous tissue oxygenation.

Blood Viscosity↗

Structured triglyceride for parenteral nutrition: meta-analysis of randomized controlled trials.

This study assessed the safety and efficacy of structured triglyceride (ST) for parenteral nutrition. A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. Clinical trials were identified from the following electronic databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Chinese Bio-medicine Database. The search was undertaken in March 2005. Language was restricted to Chinese and English. Literature references were checked at the same time. Only RCTs were extracted and evaluated by two reviewers independently of each other. The statistical analysis was performed by RevMan4.2 software which was provided by the Cochrane Collaboration. A P value of <0.05 was considered statistically significant. Ten RCTs involving 236 patients were included. Eight of them compared ST with the long-chain triglyceride (LCT), and the combined results showed that the ST had significant effect on resting energy expenditure (weighted mean difference [WMD] =1.54, 95%CI [ 1.26, 1.82], p<0.00001), plasma glycerol (WMD = 0.14, 95%CI [0.06, 0.22], P= 0.0007), free fatty acids (WMD=0.24, 95%CI [0.10, 0.37], P=0.0006), and beta-hydroxybutyric acid (WMD=0.14, 95%CI [0.06, 0.22], P=0.0007), but no differences was found regarding nitrogen balance (standardized mean difference [SMD] = 0.64, 95%CI [-0.30, 1.59], P=0.18), respiratory quotient (WMD =-0.02, 95%CI [-0.04, 0.01], P= 0.18), and plasma triglycerides (WMD = -0.10, 95%CI [-0.30, 0.10], P=0.32). Only two RCTs compared ST with the physical mixture of medium- and long-chain triglyceride (MCT/LCT), data from trials were not combined due to clinical differences between trials, and conclusions can not be drew from the present data. ST appeared to be safe and well tolerated. Further trials are required, especially compared with the MCT/LCT, with sufficient size and rigorous design.

3-Hydroxybutyric Acid↗

Marked acceleration of exogenous fatty acid incorporation into cellular triglycerides by fetuin.

Fetuin belongs to a group of fetal glycoproteins whose specific function is not known. In this study we investigated the effect of bovine fetuin on exogenous fatty acid incorporation into lipid classes by fetal rabbit aortic smooth muscle cells (SMC) and human fetal skin fibroblasts. When compared with albumin, the addition of fetuin to the culture medium caused a dramatic increase in labeled fatty acid incorporation (nanomoles/mg of protein) by SMC into triglycerides (albumin (control) 2.8 +/- 0.3 + fetuin 178.3 +/- 13.7). This effect was noted at a wide range of fetuin concentrations (0.2-5%) at oleate:fetuin molar ratios of 3.3-0.13, respectively. Similar effects were noted using human fetal skin fibroblasts with both labeled oleic and arachidonic acids (0.1 mM) as substrates (arachidonic acid incorporation into triglycerides, albumin (control) 76.9 +/- 16.2 + fetuin 684.6 +/- 64.1). Stimulation of fatty acid incorporation into di- and monoglycerides was also noted. Although the amount of unbound fatty acid in the presence of fetuin was greater than with albumin, experiments done under conditions that create identical unbound oleate levels (by varying fatty acid concentration) still showed increased fatty acid incorporation into triglycerides by SMC when exposed to fetuin. This marked effect of fetuin on triglyceride accumulation in cells was confirmed by lipid analysis, strong positive staining with oil red O, and transmission of electron microscopy. Furthermore, the potential physiological role of fetuin in terms of fatty acid and transport was attested by (a) the presence of significant amounts of free fatty acids associated with fetuin; and (b) by the stimulatory effect of fetuin, even when added to culture media containing other fatty acid carriers. These results show that (a) fetuin is far more efficient than albumin in incorporating fatty acids into cells; and (b) this might represent a novel function for fetuin during development.

Animals↗

Triglyceride turnover: a comparison of simultaneous determinations using the radioglyceride and the lipolytic rate procedures.

Two different methods of examining triglyceride turnover are described. One measures the clearance of endogenously labeled triglyceride glycerol, the radioglyceride method. The other assesses the hydrolysis of endogenous very low density lipoproteins after a primed infusion of maximal doses of heparin, the lipolytic rate. Both depend on widely different assumptions. A comparison of data obtained by both methods at the same time in single individuals with widely differing triglyceride concentrations revealed them to agree quite closely. This correspondence indirectly suggests the validity of the procedures. The procedures have been applied to show that fat-free high-carbohydrate diets accelerate triglyceride production in some humans.

Animals↗

Detection of endotoxin in triglyceride-rich lipoproteins in vitro.

Numerous investigations have been performed in which volunteers have received infusions of triglyceride-rich lipoproteins without apparent screening of the infusates for bacterial endotoxin. This study was designed to examine the capacity of triglyceride-rich lipoproteins to mask their endotoxin content in vitro as measured by a chromogenic modification of the standard Limulus assay. Lipoproteins and lipoprotein-deficient plasma were isolated from normal human plasma by sequential ultracentrifugation under apyrogenic conditions. Individual lipoproteins and a synthetic lipid emulsion were suspended in 10% lipoprotein-deficient plasma. Samples were then incubated at 37 degrees C for 4 hours with increasing concentrations of E. coli (055:B5) endotoxin and assayed for detectable endotoxin activity. The capacity to inhibit detection of endotoxin in 10% lipoprotein-deficient plasma was significantly increased (10 to 100 times) by the addition of VLDL (1.0 mg triglyceride/ml), chylomicrons (1.0 mg triglyceride/ml), or the synthetic lipid emulsion (2.5 mg triglycerides/ml). These data demonstrate that triglyceride-rich lipoproteins, and the synthetic lipid emulsion, can markedly inhibit the detection of endotoxin by the Limulus assay in vitro. In addition to the potential of harm to experimental subjects, infusion of endotoxin could vitiate kinetic studies by direct alteration of lipoprotein metabolism and by inducing changes in hepatic blood flow. Thus experimental protocols that involve the infusion of humans with triglyceride-rich lipoproteins should include detailed testing for the presence of endotoxin.

Chylomicrons↗

In vitro effect of insulin and adrenaline on lung triglyceride-lipase activity in rats.

The in vitro effect of insulin and adrenaline on the activity of lung triglyceride-lipases (alkaline and acid) has been investigated. Insulin inhibited strongly both triglyceride-lipases. Only caffein almost eliminated the inhibitory action of insulin, while adrenaline and dibutyryl cyclic adenosine monophosphate did not exhibit such an effect. It was assumed that the inhibition of lung triglyceride-lipases by insulin was effected through the activation of phosphodiesterases. On the other hand since adrenaline markedly activated lung triglyceride-lipases, this action was assumed to be carried out via the activation of lung adenylate cyclase and the increase of cyclic adenosine monophosphate.

Adenylyl Cyclases↗

Interaction of dietary saturated and polyunsaturated triglycerides in regulating the processes that determine plasma low density lipoprotein concentrations in the rat.

These studies were undertaken to determine how polyunsaturated (n-3 and n-6) and saturated triglycerides interact to regulate rates of low density lipoprotein (LDL) production and rates of receptor-dependent and receptor-independent LDL transport. Animals were fed diets containing 20% (by wt) hydrogenated coconut oil or diets in which the coconut oil was progressively removed and replaced with safflower oil or fish oil concentrate. Plasma LDL concentrations fell when either of the polyunsaturated triglycerides was substituted for saturated triglycleride in the diet; however, the reduction in LDL concentrations was greater with fish oil than with safflower oil at all ratios of polyunsaturated to saturated triglyceride that were examined. The lower plasma LDL concentrations when coconut oil was replaced with fish oil could be attributed almost entirely to a much greater increase in hepatic LDL receptor activity when fish oil was used as the substitute than when safflower oil was used as the substitute. To examine the effect of polyunsaturated triglycerides when used to supplement a high saturated fat diet rather than to replace saturated fat in the diet, animals were fed a diet containing 15% coconut oil (by wt) with or without an additional supplement of 5% fish oil or safflower oil. The addition of 15% coconut oil to low fat control diet increased the rate of LDL production causing circulating LDL levels to rise by 40%. The further supplementation of this high saturated fat diet with fish oil concentrate markedly increased hepatic LDL receptor activity causing plasma LDL concentrations to return to control values whereas supplementation with safflower oil had little effect. Thus, at least in the rat, supplementation of a high saturated fat diet with a fish oil concentrate lowers plasma LDL concentrations as effectively as removing the saturated fat from the diet, although in the former case, both the production and the receptor-dependent uptake of LDL are greatly increased.

Animals↗

Triglyceride measurements: a review of methods and interferences.

The National Cholesterol Education Program has emphasized the need to identify individuals at risk for coronary artery disease (CAD). Because increased triglycerides may be a risk factor for CAD and because triglycerides are used to estimate concentrations of low-density lipoprotein (LDL) cholesterol, which has definitely been shown to be a risk factor for CAD, it is important that reliable results be obtained. Many methods are available for measuring triglyceride concentrations in serum or plasma, but there is no definitive method that confirms the reliability of any of these procedures. Accuracy and precision guidelines are extremely difficult to determine, owing to broad biological variability both within and among individuals. Here, we review the major triglyceride quantification methods in the literature, some of the potential interference problems, and the limitations regarding standardization that should be addressed when establishing such guidelines.

Chemistry, Clinical↗

Triglyceride measurement and its relationship to heart disease.

Elevated triglycerides are clinically important owing to their direct relationship to pancreatitis, and their association with glucose intolerance, and renal and hepatic disease. Their direct role in atherosclerosis is still controversial and their inter-relationships with other lipoproteins make clarity of this issue difficult. Triglyceride measurements, as part of lipid evaluation for atherosclerotic risk, are important as they provide the only convenient and cost-effective method for routinely estimating LDL cholesterol. Their inverse relationship to HDL makes triglyceride measurements a cost-effective screening procedure. Unlike cholesterol measurements, triglycerides should always be assessed in the fasting state. Analytical methods are predominantly based on enzymatic reagent systems that reliably measure the glycerol component after fatty acid hydrolysis. Standardization (that is, accuracy) is still a major problem, while precision appears satisfactory in most clinical laboratories.

Coronary Disease↗

Genetic analysis of total cholesterol and triglycerides in a pedigree of St. Thomas rabbits.

A pedigree consisting of 103 New Zealand White hyperlipidemic and normal rabbits was used in a genetic analysis of total cholesterol and triglyceride levels to test for Mendelian control of hyperlipidemia. The founder male of this pedigree was identified through hypercholesterolemia and evidence suggested vertical transmission of a hypercholesterolemic phenotype in this pedigree, although a combined hyperlipidemia phenotype (elevated cholesterol and triglycerides) also occurred in many descendents of the original founders. Segregation analysis of quantitative measures of total cholesterol and triglycerides in this pedigree was employed to test hypotheses about Mendelian control in the presence of substantial inbreeding. A simple Mendelian model was the best explanation for triglycerides in these animals. This best fitting model was essentially co-dominant with genotypic specific variances, where the heterozygote was hypertriglyceridemic and the mutant homozygote showed even more extreme values. The observed distribution of total cholesterol was also compatible with a mixture of distinct genotypic distributions, but there was evidence of non-Mendelian transmission in this pedigree. The observed hypertriglyceridemia in these animals may reflect an abnormality of very low density lipoprotein metabolism described previously. Further studies will be required to elucidate the genetic control of hypercholesterolemia and the associated combined hyperlipidemia in these rabbits.

Animals↗

Insulin, obesity, and triglyceride interrelationships in sixteen children with familial hypertriglyceridemia.

Sixteen children with familial hypertriglyceridemia were studied to determine whether there were any distinctive insulintriglycerid-obesity relationships in pediatric familial hypertriglyceridemia. Eleven of 16 children had calculated fat mass greater than the 97th percentile for age, height, and sex. When compared with 16 normal control subjects matched for degree of obesity immunoreactive insulin and glucose response during oral glucose tolerance was similar for normal and hypertriglyceridemic children. By either simple correlation or multiple regression analysis, plasma, triglycerides did not correlate significantly with measurements of insulin or obesity in hypertriglyceridemic or normal children. Within the limits of a small sample size, and in the presence of obesity, insulin does not appear to play a predominant role in the genesis of hypertriglyceridemia in children with familial hypertriglyceridemia. With a small mean weight loss of 1.8 kg and adherence to a diet with 20% of calories as protein, 40% each as fat and carbohydrate, polyunsaturate to saturate ratio of 1.5:1, mean plasma triglycerides were reduced from 238 to 140 mg/100 ml in the 11 obese children with familial hypertriglyceridemia (P less than 0.02). Speculation In spite of the complicating role of obesity, adolescence, and the small sample size, it is interesting to note that the correlation coefficients between triglyceride and insulin/glucose area (0.36), and insulin area (0.30), although not significant (P less than 0.1), were considerably higher in hypertriglyceridemic children than in normal subjects in whom comparable correlation coefficients were 0.08 and 0.08. This infers that the potential role of insulin in triglyceride metabolism in children with familial hypertriglyceridemia might be discerned with longitudinal follow-up into adulthood.

Adolescent↗

Plasma cholesteryl ester-triglyceride transfer protein. The catalytic domain is a low molecular weight proteolipid.

The lipid transfer protein complex (LTC) isolated from human plasma by immunoaffinity chromatography transfers cholesteryl esters (CE), triglycerides, and phosphatidylcholine (PC) between lipoproteins in vitro. The molecular weight of this lipid transfer catalyst in sodium dodecyl sulfate-polyacrylamide gels was 65,000. When resolved on a gel filtration column by high performance liquid chromatography (HPLC), LTC was composed of fractions of high (greater than 150,000) to low (18,000) molecular weight, although sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of each fraction revealed bands at Mr 65,000 (major) and 52,000 (minor). The CE and triglyceride transfer activity of the low Mr HPLC fraction (1049 nmol of triglyceride/mg/h and 244 nmol of CE/mg/h) was significantly greater than that of the high Mr HPLC fraction (15-27 nmol of triglyceride/mg/h and 20-30 nmol of CE/mg/h). The PC transfer activity of the HPLC fractions was not determined. LTC proteins were separated by dialysis in acidified chloroform:methanol solution into dialysand and dialysate proteins. The dialysate contained a low Mr proteolipid, designated the catalytic domain Cd, which catalyzed CE and triglyceride transfer at equivalent rates (11.0 versus 9.5 mumol/mg/h, respectively). PC transfer activity was approximately 10% of these levels (1.5 mumol/mg/h). The dialysand consisted of a protein, designated the transfer protein TP, which facilitated CE (3.4 mumol/mg/h) preferentially over triglyceride and PC (1.0 mumol/mg/h) transfer, and a catalytically inactive protein, designated the heparin-binding domain Hd. We propose a model of the LTC protein (based on catalytic activities, monoclonal antibody reactivities, and heparin-binding capacities of the isolated proteins) in which both Hd (approximately 13 kDa) and Cd (approximately 3 kDa) originate from a single lipid transfer protein, TP.

Amino Acids↗

Apolipoprotein B synthesis in rat small intestine: regulation by dietary triglyceride and biliary lipid.

Apolipoprotein B (apoB) synthesis rates have been determined, in vivo, in rat enterocytes. Following intralumenal administration of a pulse of [3H]leucine, newly synthesized apoB was quantitated by specific immunoprecipitation and compared to [3H]leucine incorporation into total, trichloroacetic acid-insoluble protein. ApoB synthesis rates were determined after acute administration of either 0.1 or 1 g of triglyceride to fasting animals. No differences were found at any time from 90 min to 6 hr after challenge and values were not different from the basal values established in fasted controls. Animals rechallenged with triglyceride after 8 days' intake of fat-free chow also failed to demonstrate a change in intestinal apoB synthesis rate. By contrast, enterocyte content of apoB appeared to fall, temporarily, with the onset of active triglyceride flux. Groups of animals were then subjected to external bile diversion for 48 hr, a maneuver designed to remove all lumenal sources of lipid. Jejunal apoB synthesis rates fell by 43% (from 0.76% +/- 0.14 to 0.43% +/- 0.12, P less than 0.001), a change that was completely prevented by continuous replacement with 10 mM Na taurocholate. The suppression of jejunal apoB synthesis, induced by prolonged bile diversion, was reversed after 14 hr, but not 8 hr, of intralumenal perfusion with 10 mM Na taurocholate. The addition of micellar fatty acid-monoolein to the perfusate for 4 hr produced no further change in apoB synthesis. Ileal apoB synthesis rates fell by 70% (from 0.61% +/- 0.15 to 0.18% +/- 0.10, P less than 0.001) following 48 hr external bile diversion, a change that was only partially prevented by continuous bile salt replacement. These results suggest that jejunal apoB synthesis demonstrates bile salt dependence but not regulation by acute triglyceride flux. The data further suggest that key aspects of the regulation of apoB synthesis by cellular lipid flux may be mediated independently in jejunal and ileal enterocytes.

Animals↗

Synthesis of plasma triglycerides in endogenous hypertriglyceridemia.

Radioisotopic kinetic studies of triglyceride fatty acid synthesis from serum free fatty acids have been performed in 20 studies of normal and lipemic subjects. The lipemic subjects were characterized as having carbohydrate-responsive endogenous lipemia, and were classified as having either Type III or Type IV prebetalipoproteinemia. In the untreated state, triglyceride production was reduced relative to concentration of triglyceride when compared with the normal control population. In response to carbohydrate restriction an absolute reduction in triglyceride synthesis from free fatty acids was demonstrated. These data indicate that overproduction cannot be importantly implicated as the etiology of this form of endogenous lipemia. The patients thus represent a pathophysiological entity which is distinct from the normal physiological lipemia induced by carbohydrate feeding in which overproduction is reported to be the initiating event.

Adolescent↗

Respiratory failure in acute pancreatitis: a possible role for triglycerides.

Respiratory failure is a frequent complication of acute pancreatitis. Two clinical studies of this association have demonstrated a high incidence of concomitant hypertriglyceridemia. Experimental studies were carried out using an ex vivo, isolated, perfused, ventilated, canine pulmonary lobe to evaluate the effects of triglyceride elevations on pulmonary mechanics and gas exchange. Control lobes perfused for a four hour period remained stable. When 5g and 10g of triglyceride were added to the perfusate, the lobes became grossly edematous and hemorrhagic. Intrapulmonary shunting developed (23 and 46%), weight gain occurred (130 and 189g), effective compliance decreased, and the pressure-volume deflation curves became abnormal. Free fatty acid (FFA) levels increased markedly during the perfusion periods. When small quantities of FFA were infused directly into the pulmonary artery, similar changes, but less severe, occurred. These studies demonstrate that triglyceride elevations are capable of adversely affecting pulmonary gas exchange and mechanics. Such changes probably occur secondary to FFA release. These data thus add support to the concept that the respiratory insufficiency that is seen in acute pancreatitis could be mediated through triglyceride elevations.

Acute Disease↗