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PubMed2002

Postprandial plasma ApoB-48 levels are influenced by a polymorphism in the promoter of the microsomal triglyceride transfer protein gene.

The microsomal triglyceride transfer protein (MTP) plays a key role in the secretion of apolipoprotein B (apoB)-containing lipoproteins. The rare variant of a functional polymorphism in the promoter region of the MTP gene has been associated with elevated transcriptional activity of the gene in vitro (MTP-493G/T). With use of a "recruit-by-genotype" approach, we investigated one of the potentially complex phenotypes of this polymorphism, the appearance in plasma of apoB-48 after a meal intake. A total of 12 homozygous carriers of the rare MTP-493T variant were identified from a population-based screening of 50-year-old healthy white men. All subjects were of the apoE3/3 genotype. Along with 48 baseline well-matched heterozygotes (n=24) plus homozygotes (n=24) for the common variant, they were given a standardized oral fat meal. Postprandial plasma concentrations of apoB-48 were determined by the combination of density gradient ultracentrifugation and analytical SDS-PAGE. The postprandial plasma concentrations of triglycerides did not differ between the groups, but homozygous carriers of the rare MTP-493T variant showed a >100% greater increase in apoB-48 in the smallest (Svedberg flotation rate constant 20 to 60) triglyceride-rich lipoprotein fraction (P=0.005). These data support the notion that elevated transcriptional activity of MTP leads to an increased generation of the smallest triglyceride-rich lipoprotein from the intestine.

Analysis of Variance↗

PubMed1976

Effects of cord factor on liver lipid: accumulation triglycerides.

A single intraperitoneal injection of cord factor induced a remarkable increase in the amounts of triglycerides in liver. This effect was specific for cord factor among various lipid fractions of tuberclebacilli. Other lipid species of liver than triglycerides were not affected by cord factor injection. The accumulation of triglycerides became evident 16 to 24 hours after the cord factor injection and reached the maximum at 48 hours. As small a quantity as 12.5 mug of cord factor effectively induced the increase of triglycerides in liver.

Animals↗

PubMed1972

Precursor-product relationship between pools of very low density lipoprotein triglyceride.

The process of removal of triglyceride from the plasma may involve a sequential conversion of larger to smaller glyceride-rich lipoproteins. This has been studied within the species of lipoproteins comprising the very low density lipoproteins (VLDL) which transport the bulk of endogenously formed triglyceride. Palmitic acid-(14)C which was used to label the plasma glycerides was administered either as a prolonged constant infusion or as a pulse label. The specific activity-time curves of triglyceride fatty acids (TGFA) were analyzed both in total VLDL and in two subfractions of VLDL. The nature of the curves for total VLDL that were observed during the constant infusions were consistent with slow isotopic equilibration of precursors of VLDL-TGFA or with the presence of a precursor-product relationship between different components of VLDL-TGFA. The curves did not indicate any detectable differences in (fractional) turnover rates of independently metabolized pools of VLDL-TGFA. Differences in the specific activity-time curves of TGFA in two subfractions of VLDL (Sf > 100 and Sf 20-100) were consistent with a precursor-product relationship between TGFA in the two subfractions; again there was no indication of significant differences in (fractional) turnover rates. The specific activity-time curves of TGFA in the two subfractions of VLDL that were obtained with single injections of radio-palmitate showed a consistent difference in the rates at which TGFA became labeled in the two subfractions, being slower in the Sf 20-100 fraction. The findings from all experiments when considered together, were compatible with a precursor-product relationship that suggested that larger VLDL were converted to progressively smaller species as triglyceride was being removed.

Adolescent↗

PubMed1973

Diurnal patterns of triglycerides, free fatty acids, blood sugar, and insulin during carbohydrate-induction in man and their modification by nocturnal suppression of lipolysis.

Previous studies have shown that carbohydrate induction of hypertriglyceridemia in normal subjects occurs at night and appears to be related to a rise of free fatty acids after diurnal feeding of high-carbohydrate formula diet. The present investigation was undertaken to observe the effect on 24-h triglyceride, free fatty acid, blood sugar, and plasma insulin profiles of inhibition of nocturnal lipolysis by glucose or nicotinic acid in normal subjects and in patients with type IV hyperlipoproteinemia. In 10 normal subjects and 10 patients with primary type IV hyperlipoproteinemia, plasma triglyceride, free fatty acid, blood sugar, and insulin levels were followed in short intervals for 24 h while a 2,400 cal, 80% carbohydrate, fat-free formula diet was given in six equal portions during the day (control experiments). This procedure was repeated in the same subjects, 10 of whom (5 normal subjects and 5 patients) received additional feedings of glucose between 2000 and 0600 h while the other 10 persons (5 normal subjects and 5 patients) were given nicotinic acid by intravenous infusion during the same time interval. Both procedures resulted in maintained lowering of free fatty acid levels over 24 h. Mitigation of carbohydrate-induced hypertriglyceridemia appeared to result from the additional glucose in normals and in patients. Nicotinic acid abolished the nocturnal rise of plasma triglyceride levels which in the control studies of normal subjects had resulted in approximate doubling of triglyceride levels in 24 h. The effectiveness of nicotinic acid in inhibiting nocturnal lipolysis and preventing carbohydrate-induction of hypertriglyceridemia might have consequences for management of endogenous hypertriglyceridemia.

Adult↗

PubMed1975

Characterization of remnants produced during the metabolism of triglyceride-rich lipoproteins of blood plasma and intestinal lymph in the rat.

The metabolism of intravenously injected large and small chylomicrons from intestinal lymph and of very low density lipoproteins from blood plasma was studied in functionally eviscerated "supradiaphragmetic" rats. For studies with lymph lipoproteins, recipient animals were injected with 4-amino-pyrazolopyrimidine 18 h before injection of lipoprotein to prevent secretion of very low density lipoproteins into their blood plasma. In all cases, most of the triglycerides (labeled with 14C) were rapidly metabolized, whereas cholesteryl esters (labeled with 3H) persisted in the blood. Most of the cholesteryl esters remained in smaller "remnant" lipoproteins, less dense that 1.006, which retained an apparently spherical shape, as determined by electron microscopy of negatively stained preparations. Whereas the diameters and chemical compositions of large chylomicrons were substantially different from those of small chylomicrons and very low density lipoproteins, all remnants were similar in these respects. Average remnant diameters were 400-600 A and remnants were enriched in cholesteryl esters and in protein insoluble in tetramethylurea. In addition to triglycerides, remnants were depleted of phospholiarticle size, the composition of remnants, like that of their precursors, was consistent with the "pseudomicellar" model of lipoproteins, in which a core of nonpolar lipids is covered by a monolayer of polar lipids and protein. These results domonstrate the fundamental similarity of the initial step in the metabolism of triglyceride-rich lipoproteins from intestinal mucosa and liver and show that loss of triglycerides from the core of the particles is accompanied by removal of polar components from the surface.

Animals↗

PubMed1985

Bovine milk lipoprotein lipase transfers tocopherol to human fibroblasts during triglyceride hydrolysis in vitro.

Lipoprotein lipase appears to function as the mechanism by which dietary vitamin E (tocopherol) is transferred from chylomicrons to tissues. In patients with lipoprotein lipase deficiency, more than 85% of both the circulating triglyceride and tocopherol is contained in the chylomicron fraction. The studies presented here show that the in vitro addition of bovine milk lipoprotein lipase (lipase) to chylomicrons in the presence of human erythrocytes or fibroblasts (and bovine serum albumin [BSA]) resulted in the hydrolysis of the triglyceride and the transfer of both fatty acids and tocopherol to the cells; in the absence of lipase, no increase in cellular tocopherol was detectable. The incubation system was simplified to include only fibroblasts, BSA, and Intralipid (an artificial lipid emulsion containing 10% soybean oil, which has gamma but not alpha tocopherol). The addition of lipase to this system also resulted in the transfer of tocopherol (gamma) to the fibroblasts. Addition of both lipase and its activator, apolipoprotein CII, resulted in a further increase in the cellular tocopherol content, but apolipoprotein CII alone had no effect. Heparin, which is known to prevent the binding of lipoprotein lipase to the cell surface membrane, abrogated the transfer of tocopherol to fibroblasts without altering the rate of triglyceride hydrolysis. Thus, in vitro tocopherol is transferred to cells during hydrolysis of triglyceride by the action of lipase, and for this transfer of tocopherol to occur, the lipase itself must bind to the cell membrane.

Animals↗

PubMed1993

Metabolism of triglyceride-rich lipoproteins during alimentary lipemia.

The metabolism of chylomicron remnants and VLDL was studied in healthy controls and normo- (NTG) and hypertriglyceridemic (HTG) patients with coronary artery disease after intake of an oral fat load. Specific determination of apo B-48 and B-100 enabled separation of the respective contribution of the two lipoprotein species. The postprandial plasma levels of small (Sf 20-60) and large (Sf 60-400) chylomicron remnants increased in controls and NTG patients. In contrast, only large chylomicron remnants increased in the HTG patients. An increase of large VLDL was seen in response to the oral fat load in all groups, whereas small VLDL were either unchanged in the controls and the NTG patients, or decreased in the HTG patient group. The whole plasma concentration of C apolipoproteins was essentially uninfluenced by the oral fat load, whereas the content in large triglyceride-rich lipoproteins paralleled the apo B elevations in controls and NTG patients. An even more prominent increase of apo B in large triglyceride-rich lipoproteins in the HTG group was not accompanied by an increase of C apolipoproteins. These findings indicate that chylomicrons compete with VLDL for removal of triglycerides by lipoprotein lipase and that the postprandial metabolism of triglyceride-rich lipoproteins is severely defective in hypertriglyceridemia.

Apolipoproteins B↗

PubMed1999

Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice.

A deficiency in microsomal triglyceride transfer protein (MTP) causes the human lipoprotein deficiency syndrome abetalipoproteinemia. However, the role of MTP in the assembly and secretion of VLDL in the liver is not precisely understood. It is not clear, for instance, whether MTP is required to move the bulk of triglycerides into the lumen of the endoplasmic reticulum (ER) during the assembly of VLDL particles. To define MTP's role in hepatic lipoprotein assembly, we recently knocked out the mouse MTP gene (Mttp). Unfortunately, achieving our objective was thwarted by a lethal embryonic phenotype. In this study, we produced mice harboring a "floxed" Mttp allele and then used Cre-mediated recombination to generate liver-specific Mttp knockout mice. Inactivating the Mttp gene in the liver caused a striking reduction in VLDL triglycerides and large reductions in both VLDL/LDL and HDL cholesterol levels. The Mttp inactivation lowered apo B-100 levels in the plasma by >95% but reduced plasma apo B-48 levels by only approximately 20%. Histologic studies in liver-specific knockout mice revealed moderate hepatic steatosis. Ultrastructural studies of wild-type mouse livers revealed numerous VLDL-sized lipid-staining particles within membrane-bound compartments of the secretory pathway (ER and Golgi apparatus) and few cytosolic lipid droplets. In contrast, VLDL-sized lipid-staining particles were not observed in MTP-deficient hepatocytes, either in the ER or in the Golgi apparatus, and there were numerous cytosolic fat droplets. We conclude that MTP is essential for transferring the bulk of triglycerides into the lumen of the ER for VLDL assembly and is required for the secretion of apo B-100 from the liver.

Alleles↗

PubMedDate not supplied

Effect of fat emulsions containing medium-chain triglycerides and glucose on ketone body production and excretion.

The parenteral application of fat emulsions containing medium-chain triglycerides results in an increase of ketone bodies as expression of the rapid metabolism of medium-chain triglycerides. Although ketoacidosis could not be watched, it should be of advantage to reduce the ketonemia. This might be reached by application of carbohydrates. The simultaneous infusion of glucose--given to 10 healthy persons--together with a 10% fat emulsion containing 75% medium-chain triglycerides almost completely inhibited the increase of ketone bodies in serum and its urinary excretion. Other prosperous metabolic effects, eg, the rapid clearance of the triglycerides from the serum were not affected by this regimen.

3-Hydroxybutyric Acid↗

PubMedDate not supplied

Elimination and metabolism of a fat emulsion containing medium chain triglycerides (lipofundin MCT 10%).

Medium chain triglycerides (MCT) are supposed to be advantageous on account of rapid energy supply in parental nutrition. However, data on the elimination rate of MCT-containing emulsions during an intravenous fat-tolerance test (IVFTT) are scarce. We performed this test (0.1 g lipid/kg body weight) in 18 young healthy volunteers (nine females and nine males) using Lipofundin MCT 10% (50% MCT; egg phospholipids as emulsifier). Our results indicate that both elimination and metabolization of the emulsion are fast: a prompt decrease of light-scattering index and of triglyceride concentrations in serum, an immediate appearance of post-load fatty acids and of beta-hydroxybutyrate were observed. This was in good agreement with the findings obtained during 6-hr infusions in the same probands. Fractional elimination rates k2 obtained from light-scattering indices are 7.29 +/- 2.73%/min in males and 11.59 +/- 3.38%/min in females, indicating a higher removal capacity in women. In the same subjects, the corresponding k2 values for Lipofundin S 10% (containing only long chain triglycerides) were higher, reflecting an elimination rate that is faster due to the use of soya bean phospholipids as emulsifier. In comparison, k2 values based on the course of the triglyceride concentrations are generally lower.

3-Hydroxybutyric Acid↗

PubMedDate not supplied

Arterial deepvenous difference of lipoproteins in skeletal muscle of patients in postoperative state: effects of medium chain triglyceride emulsion.

The effect of fat infusion with medium chain triglycerides (MCT) and long chain triglycerides (LCT) on serum lipoproteins before and after passage through the skeletal muscle was investigated with the forearm technic in eight patients after abdominal operation. All lipoprotein fractions were enriched with triglycerides and phospholipids from infused artificial fat particles with the consequence of significantly increased ratios of TG/PL and TG/apo B in VLDL, of TG/apo B in LDL and TG/apo A-I in HDL. Uptake and release of lipoprotein components by skeletal muscle are given by arterial-deepvenous differences considering the blood flow rates. The positive arterial-deepvenous difference of VLDL triglycerides after 4-hr infusion is interpreted as cleavage and uptake of infused MCT by the muscle. The release of LDL is more pronounced after the fat infusion than before, suggesting a degradation and enhanced catabolism of artificial fat particles. HDL release may be also a consequence of catabolism of artificial TG/PL-particles. These results indicate an uptake of MCT/LCT emulsion by the skeletal muscle.

Adult↗

PubMedDate not supplied

Efficacy of different triglycerides in total parenteral nutrition for preventing atrophy of the gut in traumatized rats.

BACKGROUND: The efficacy of different fat emulsions as components of a total parenteral nutrition (TPN) regimen on the integrity of the gut was assessed in traumatized rats. With the release of the short-chain fatty acids butyric or propionic acid during the hydrolysis of a structured triglyceride containing butyric acid (C4-L-C4-TG) or the beta-oxidation of nonanoic acid from trinonanoin (C9TG), respectively, the infusion of these two triglycerides was supposed to reveal positive effects against the TPN-induced atrophy of the intestine. METHODS: After 3 days of fiber-free liquid diet, rats were traumatized (laparotomy) and catheterized. Afterwards they received equicaloric TPN that delivered 1008 kJ (241 kcal)/kg of body weight per day and 30% nonprotein calories as fat emulsion. The four fat emulsions tested in four groups of six animals contained either long-chain triglycerides (LCT), medium-chain triglycerides (MCT)-LCT (1:1), C9TG/LCT (1:1) or C4-L-C4-TG. Animals of a control group were infused with isovolemic 0.9% NaCl solution and were offered oral standard chow. RESULTS: After 7 days of MCT/LCT administration, the mass-to-length ratio of the total small bowel as well as the masses of mucosa/submucosa and muscularis/serosa in 10-cm segments of the distal half of the small bowel were significantly higher than that found in the other TPN groups or not different from controls. Histometric measurement of the villus height in the ileum revealed no statistically significant differences from controls for the rats of the MCT/LCT and C4-L-C4-TG groups. In the colon, no statistically significant differences between TPN groups were found for either parameter. CONCLUSIONS: Within the tested fatty substrates the MCT/LCT fat emulsion revealed less structural impairments in the distal half of the small bowel regarding mucosa/submucosa (mass and villus height), but also muscularis/ serosa (mass).

Animals↗

PubMed1996

Association of serum cholesterol and triglyceride levels with agitation and cognitive function in a geropsychiatry unit.

Several studies have reported an association between aggression and cholesterol levels. The purpose of this study was to investigate the relationship of serum cholesterol and triglyceride levels with aggression and cognitive function in elderly inpatients. One hundred ten patients consecutively admitted to the Geriatric Psychiatry inpatient unit at Houston's Veterans Affairs Hospital received comprehensive evaluations by a multidisciplinary team. Fasting serum cholesterol and triglyceride levels were obtained within 3 days of admission. In addition, two geriatric psychiatrists administered the Mini-Mental State Examination (MMSE) and the Cohen-Mansfield Agitation Inventory (CMAI). Correlation coefficients were calculated between lipid levels, CMAI total and subscale scores, and MMSE scores. Multiple linear-regression analyses were done to further investigate the relation between lipid concentrations and various confounders. We found no significant correlation between serum triglyceride levels and MMSE, CMAI total, and CMAI factor scores. In addition, we found a significant positive correlation between serum cholesterol levels and physical nonaggressive behavior, and a significant negative correlation between serum cholesterol levels and MMSE scores. We found no relationship between aggressive behavior and serum cholesterol or triglyceride levels. However, an association between high cholesterol levels and agitation exists, which may be mediated by the association between high cholesterol levels and impaired cognition.

Aged↗

PubMed1994

Atherogenicity of triglyceride-rich lipoproteins.

The measurement of plasma triglyceride levels further refines the estimation of the risk of coronary heart disease in patients with either high levels of low-density-lipoprotein cholesterol or a high ratio of low-density-lipoprotein to high-density-lipoprotein cholesterol. Plausible mechanisms underlying the role of triglyceride-rich lipoproteins in the pathogenesis of coronary heart disease include the lipid loading of macrophages and accelerated thrombosis resulting from increases in both procoagulant and antifibrinolytic activity. Further research should include methods for better quantifying atherogenic subspecies of triglyceride-rich lipoproteins and intervention studies designed to assess the effect on the occurrence of coronary heart disease of lowering triglyceride or increasing HDL-cholesterol levels.

Arteriosclerosis↗

PubMed1996

Association of body mass index, blood pressure and serum levels of triglycerides and high-density lipoprotein cholesterol in childhood with the insulin sensitivity index in young adulthood: a 13-year follow-up.

BACKGROUND: Tracking of body mass index (BMI), blood pressure and serum lipids from childhood to adulthood has been demonstrated in previous studies. Whether these factors are associated with the insulin-sensitivity index measured in young adulthood (ISIadult) remains undetermined. OBJECTIVES: To determine whether any association exists between the ISIadult and BMI, blood pressure and plasma lipids measured in childhood (1979). METHODS: The study included 227 unrelated white subjects (aged 18-32 years). Their ISIadult were measured in 1992/93 with a combined intravenous glucose (0.3 gl/kg body weight) and tolbutamide (3 mg/kg body weight) tolerance test. BMI, blood pressure and blood lipids were measured in 1979 and again in 1992/93. RESULTS: In men, plasma high-density lipoprotein cholesterol (HDLC) in 1979 (rs = 0.25, F = 0.006) was positively associated with ISIadult and plasma triglyceride measured in 1979 (rs = -0.34, P = 0.001). BMI (rs = -0.29, P = 0.002) and systolic blood pressure, both measured in 1979 (rs = -0.29, P = 0.002) were associated negatively with ISIadult. In women, plasma HDLC measured in 1979 was associated positively and significantly with ISIadult (rs = 0.21, P = 0.024) and BMI measured in 1979 was associated significantly and negatively with ISIadult (rs = -0.22, P = 0.018). Plasma triglyceride or systolic blood pressure, both measured in 1979, were not associated with ISIadult. In gender-stratified multiple-regression analyses [controlling for waist circumference(adult) maximal aerobic capacity (VO2max(adult)), age and women's use of oral contraceptives], plasma HDLC measured in 1979 was associated significantly with ISIadult in men (P = 0.026) but not in women (P = 0.066). A negative association was found between plasma triglyceride measured in 1979 and ISIadult (P = 0.045) in men, but not in women (P = 0.30). BMI, total cholesterol and systolic and diastolic blood pressure, all measured in 1979, were not associated with ISIadult. CONCLUSION: Low plasma HDLC, high plasma triglyceride and high BMI in childhood are associated with low insulin-sensitivity index values in young adulthood.

Adolescent↗

PubMed2006

Use of filter paper stored dried blood for measurement of triglycerides.

Adaptation of assays on dried blood has advantages of ease of collection, transportation, minimal invasiveness and requirement of small volume. A method for extraction and estimation of triglyceride from blood spots dried on filter paper (Whatman no. 3) has been developed. A single dried blood spot containing 10 muL blood was used. Triglyceride was efficiently extracted in methanol from blood dried on filter paper by incubation at 37 degrees C for two hours with gentle shaking. For the estimation, a commercially available enzymatic method was used. Blood spot assays showed mean intra and inter assay coefficient of variance of 6.0% and 7.4% respectively. A comparison of paired whole blood spots and plasma samples (n = 75, day 0) gave an intraclass correlation of 0.96. The recovery was 99.6%. The dried blood triglyceride concentrations were stable for one month when the filter discs were stored at room temperature (16-28 degrees C). Storage of filters at 4 degrees C extended the stability and triglycerides could be quantitatively recovered after 3 months of storage.

Blood Specimen Collection↗

PubMed2004

Triglyceride levels are ethnic-specifically associated with an index of stearoyl-CoA desaturase activity and n-3 PUFA levels in Asians.

Accumulated evidence suggests that hypertriglyceridemia (HTG) is independently associated with an increased incidence of cardiovascular disease. The hypotriglyceridemic effects of n-3 PUFAs have been confirmed in Caucasians, but the effect in Asians is less clear. Recent evidence indicates that stearoyl-CoA desaturase (SCD) activity induced with high-carbohydrate diets increases plasma triglyceride levels. We investigated the relationship between triglyceride levels and the ratio of plasma oleic acid to stearic acid (the 18:1/18:0 ratio), a plasma marker of SCD activity, and n-3 PUFAs in 411 Japanese, 418 Korean, and 251 Mongolian adults. The Japanese and Koreans had higher values for triglyceride than their Mongolian counterparts, despite lower body mass index values for the Japanese and Koreans. The Japanese and Koreans ate fish more frequently and had remarkably higher values for n-3 PUFAs than did the Mongolians. Multiple regression analysis showed that triglyceride levels had a great magnitude of correlation with the increases in 18:1/18:0 ratio for the Japanese and Mongolians, and n-3 PUFAs remained significant for the Mongolians. HTG is ethnicity-specifically associated with an increase in the 18:1/18:0 ratio and a decrease in n-3 PUFA in plasma for Japanese, Koreans, and Mongolians.

Adult↗

PubMed2005

The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus.

Statins decrease triglycerides (TGs) in addition to decreasing low density lipoprotein-cholesterol. Although the mechanism for the latter effect is well understood, it is still unclear how TG decrease is achieved with statin therapy. Because hypertriglyceridemia is common in obese patients with type 2 diabetes mellitus, we studied triglyceride-rich lipoprotein triglyceride (TRL-TG) turnover in 12 such subjects using stable isotopically labeled glycerol. The diabetic subjects were studied after 12 weeks of placebo and after a similar course of therapy with simvastatin (80 mg daily) in a single-blind design. The results were compared with those from six nonobese nondiabetic control subjects. Simvastatin therapy reduced serum TGs by 35% in the diabetic subjects. Compared with the control subjects, TRL-TG secretion was almost 2-fold higher in the diabetic subjects (45.4 +/- 4.9 vs. 24.4 +/- 1.9 micromol/min; P < 0.002) and was unaffected by simvastatin therapy. However, TRL-TG clearance was significantly increased in the diabetic subjects during simvastatin treatment compared with placebo (0.25 +/- 0.03 vs. 0.16 +/- 0.02 pools/h; P < 0.002). This change was accompanied by a 49% increase in preheparin plasma lipase activity (P < 0.03) and a 21% increase in postheparin LPL activity (P < 0.01). Together, these findings provide strong evidence that the effect of statins on serum TGs is related to an increase in LPL activity, resulting in accelerated delipidation of TRL particles. The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus.

Adult↗