Triglyceride Content Of Low Density Lipoprotein Research Articles

Specific Nuclear Magnetic Resonance Lipoprotein Subclass Profiles and Central Arterial Stiffness in Type 1 Diabetes Mellitus: A Case Control Study.

Background: Dyslipidemia has been associated with vascular complications of type 1 diabetes mellitus (T1DM). We examined the proton nuclear magnetic resonance (NMR)-assessed lipoprotein subclass profiles in subjects with T1DM compared with those of healthy subjects and assessed the potential relationship of these profiles with arterial stiffness. Methods: Eighty-four participants with T1DM of at least 10 years duration and no clinical cardiovascular disease (age: 35–65 years; 50% men) and 42 healthy participants were evaluated for: (1) clinical and anthropometric data (including classical cardiovascular risk factors), (2) insulin sensitivity by estimated glucose disposal rate, (3) microvascular complications, (4) NMR-assessed lipoprotein subclass profile, and (5) arterial stiffness (aortic pulse wave velocity). Results: Participants with T1DM had an apparently better conventional lipid profile than healthy participants, but with significant differences in NMR-assessed lipoprotein profiles such as higher triglyceride content of low-density lipoprotein (LDL) and high-density lipoprotein (HDL). In healthy participants, arterial stiffness was associated with NMR-based LDL subclasses. By contrast, in T1DM participants, arterial stiffness was independently associated mainly with NMR-based very-low-density lipoprotein (VLDL) subclasses: positively with total VLDL particles (and subclasses) and VLDL triglyceride content, and negatively with LDL and HDL particle sizes. These results were maintained after adjustments for classical cardiovascular risk factors. Conclusions: Subjects with T1DM, while having an apparently better conventional lipid profile than healthy controls, presented significant alterations in their NMR-assessed lipoprotein profile. The association between arterial stiffness and NMR-assessed lipoprotein profiles also differed in both groups. These results support a potential role of the identified differences in the residual cardiovascular risk in T1DM.

Treatment of primary mixed hyperlipidemia with etophylline clofibrate: effects on lipoprotein-modifying enzymes, postprandial lipoprotein metabolism, and lipoprotein distribution and composition

In 17 patients with primary mixed hyperlipidemia we studied levels and composition of lipoproteins in fasting plasma, lipoprotein-modifying enzymes, and postprandial lipoprotein metabolism after an oral fat-tolerance test supplemented with vitamin A before, and 12 weeks after treatment with etophylline clofibrate. With treatment, fasting plasma cholesterol, triglycerides, and the levels of very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL) decreased significantly; high density lipoprotein (HDL) cholesterol increased significantly. Treatment caused also an increase in the protein content of IDL, a decrease in the triglyceride content of LDL, and an increase in the size of LDL as assessed by gradient gel electrophoresis. Concentrations of triglycerides, chylomicrons, and chylomicron remnants after an oral fat load supplemented with vitamin A decreased by 33%, 30%, and 6%, respectively ( P < 0.005; P < 0.01; and P < 0.05). The activity of lipoprotein lipase and hepatic lipase in postheparin plasma increased by 51% and 45%, respectively ( P < 0.01; P < 0.05). We found a decrease in the mass concentration of cholesteryl ester transfer protein ( P < 0.05). Stepwise multiple regression analysis showed that the triglyceride content of LDL is determined primarily by fasting triglycerides ( r = +0.53, P < 0.05; baseline) and cholesteryl ester transfer protein ( r = +0.49, P < 0.05; 12 weeks); in contrast, the triglyceride content of HDL 3 is determined exclusively by accumulation of postprandial triglycerides ( r = +0.67; P < 0.05; baseline) and postprandial chylomicrons ( r = +0.87; P < 0.005; 12 weeks). We conclude that hypolipidemic treatment with etophylline clofibrate favorably affects the cardiovascular risk factor profile in primary mixed hyperlipidemia.

Oxidation of low density lipoproteins from patients with renal failure or renal transplants

Peroxidation of low density lipoproteins (LDL) may be involved in the development of atherosclerosis which is prevalent in patients with chronic renal failure and renal transplant recipients. We determined the copper ion catalyzed oxidation in vitro, vitamin E content, and chemical and fatty acid composition of LDL isolated from 38 patients with renal disease and 15 healthy subjects. Also the acute effect of hemodialysis treatment on LDL oxidation variables was tested. The lag time in conjugated diene formation during oxidation was significantly (P = 0.011) shorter in LDL from renal transplant recipients (66 min, N = 18) mainly due to significantly (P < 0.05) shorter times in women (47 min, N = 7), compared with healthy subjects (83 min, N = 15), patients on hemodialysis (91 min, N = 13) and patients treated by continuous ambulatory peritoneal dialysis (CAPD) (82 min, N = 7). The maximum rate and the extent of LDL oxidation were significantly (P < 0.01) lower in all patients with renal disease compared with healthy subjects. The triglyceride content of LDL was significantly (P < 0.001) higher in women with kidney grafts (7.3%) compared with levels in the corresponding men (5.3%) and healthy women (5.0%), and was correlated significantly with the lag time in LDL oxidation in renal transplant recipients (Spearmans r = -0.502, P = 0.034). The percentage oleic acid in LDL was significantly higher (P = 0.002) and the percentage linoleic acid was significantly lower (P = 0.046) in patients with renal disease, and may largely account for their lower rates and extent of LDL oxidation. Levels of the LDL oxidation variables and organic lipid peroxide content of LDL were not significantly different before and after hemodialysis and 24 hours later. These results suggest that LDL from women with renal transplants may be abnormally susceptible to oxidation possibly due to increased triglyceride content.

The influence of the triglyceride content of low density lipoprotein on the interaction of apolipoprotein B-100 with cells.

To study the effect of triglyceride content of low density lipoprotein (LDL) on its physicochemical and biological properties, we have depleted the triglyceride by incubation with hepatic lipase (HL-LDL) and raised the triglyceride by incubation of HL-LDL with very low density lipoprotein and lipoprotein-deficient serum. HL-LDL was taken up by human monocyte-derived macrophages and by human skin fibroblasts at an increased rate compared to untreated LDL. Incubation of the various LDL preparations revealed that cellular LDL degradation as well as LDL-mediated cholesterol esterification were inversely related to the triglyceride content of the LDL preparation. Modification of the triglyceride content of LDL also was associated with changes in the free fatty acid content, but the interaction of the LDL with cells was unaffected by the level of this component. The triglyceride content of LDL was found to be reciprocally related to the number of free lysine amino groups of LDL apolipoprotein B (apoB) which could be labeled with trinitrobenzenesulfonic acid. 13C-Nuclear magnetic resonance (NMR) spectra of native LDL and HL-LDL samples containing [13CH3]2 lysine residues formed by reductive methylation (11-13% modification) showed that the arrangement of apoB lysines is perturbed by the exposure to hepatic lipase. The ratio of labeled lysines with pK 8.9 to those with pK 10.5 exposed on the surface of LDL particles was decreased by about 40% by lipase treatment. These effects are apparently due to changes in local apoB conformation because circular dichroism spectra revealed that the average secondary structure of the entire apoB molecule is the same in native LDL and HL-LDL. The triglyceride content of LDL reciprocally affected its binding to a monoclonal antibody which recognizes epitopes around the LDL receptor binding domain of apoB. The above evidence indicates that modulation of the core triglyceride and possibly also surface phospholipid content of LDL can alter the conformation of apoB on the surface of the particle, thereby influencing the interaction with cell surface LDL receptors.

Effect of saturated and polyunsaturated fat diets on the composition and structure of human low density lipoproteins

We have studied the effect of diets of saturated and polyunsaturated fat on the composition, structure and thermal behavior of human plasma low density lipoproteins (LDL). We find that relative to a saturated fat diet one of polyunsaturated fat produces: 1. (1) An increase. in the unsaturated acyl content of all lipid classes of LDL. 2. (2) An increase in the triglyceride content of LDL. 3. (3) A decrease in the temperature of the thermotropic liquid crystal to isotropic liquid phase transition of LDL. 4. (4) No effect on the temperature of LDL denaturation. In spite of major changes in the fatty acid composition of the major lipid of LDL, cholesteryl esters, the thermal properties of LDL are dominated by their triglyceride content. Since a polyunsaturated fat diet raised LDL triglyceride levels, our calorimetric and spectroscopic results suggest that the thermal properties and the structure of LDL at 37°C are sensitive to the composition of dietary fat.

Discrepancies in the catabolic pathways of rat and human low density lipoproteins as revealed by partial hepatectomy in the rat

The serum decay of iodine-labeled low density lipoprotein (LDL) was measured in rats 2–8 h after partial hepatectomy or sham-operation. In sham-operated rats homologous LDL showed a biexponential decay with t 1 2 ' s of 0.27 ± 0.02 h and 4.3 ± 0.8 h for the initial rapid phase and the slow phase, respectively. After partial hepatectomy the t1/2 of the rapid phase was unchanged, while the t 1 2 of the slow phase increased to 10.3 ± 1.0 h ( P < 0.01). The fractional catabolic rate (F.C.R.) was decreased by 62% (from 4.8 ± 0.9 to 1.8 ± 0.2/day), a % comparable to the amount of liver removed. The level of serum LDL is slightly elevated (19%), if measured 8 h after partial hepatectomy. Chemical analysis shows that the triglyceride content of LDL decreases from 9.4 ± 2.3% in control rats to 3.7 ± 0.9% after partial hepatectomy. Human iodine-labeled LDL shows a monoexponential decay from rat serum with a t sol1 2 of 9.4 ± 0.7 h, which is not affected by partial hepatectomy. The F.C.R. is low in both sham-operated and hepatectomized rats (1.8 ± 0.1 vs. 1.9 ± 0.1/day). The % of the injected rat LDL radioactivity recovered in the liver of control rats is twice as high as that of human LDL, as measured 6 h after the injection; at this time the serum radioactivity is much lower in the case of rat LDL. Partial hepatectomy did not change the levels of extrahepatic tissue radio-activities significantly. It is concluded that the liver determines the catabolic rate of homologous LDL-apoproteins in the rat. In contrast, the slow degradation of human LDL-apoprotein is probably located extrahepatically.

Plasma lipoprotein profile and composition in White Carneau and Show Racer breeds of pigeons

Plasma lipoprotein profile and composition in atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons were investigated while consuming a regular pigeon chow diet free of cholesterol. Plasma was studied by analytical and preparative ultracentrifugation and paper electrophoresis. Lipid composition of each lipoprotein was determined by combined TLC-GLC techniques. The major plasma lipoprotein of both breeds was high density lipoprotein (HDL) with some low density lipoprotein (LDL) and no very low density lipoprotein (VLDL). Cholesterol was mainly found in the HDL in both breeds (71.7%), and no difference was noticed in the total cholesterol content of whole plasma or in various lipoproteins. The LDL fraction in White Carneaux showed a significantly lower (P less than 0.05) percentage of cholesterol esters compared with Show Racers (58.63 +/- 4.9 in White Carneaux vs. 72.12 +/- 2.1 in Show Racers). In LDL, the percentage of the triglyceride concentration in White Carneaux was significantly lower (P less than 0.01) than that of Show Racers while the percentage of protein content in White Carneaux was higher than in Show Racers. No significant differences were observed in fatty acid composition of steryl esters phospholipids, and triglycerides in the lipoprotein fractions of the two breeds. These studies show important differences in the cholesterol esters, protein, and triglyceride content of LDL in the atherosclerosis-susceptible breed of pigeons.