Normotriglyceridemic Individuals Research Articles

Prior arm-crank exercise has no effect on postprandial lipaemia in nondisabled adults

A single bout of cycling or running performed in the evening can reduce postprandial lipaemia (PPL) the following morning, although this is currently unknown for upper-body exercise. The aim of this study was to determine if a bout of arm crank exercise (high-intensity interval [HIIE] or moderate-intensity continuous [MICE]), can attenuate PPL in non-injured individuals. Eleven healthy and recreationally active participants (eight males, three females; age: 27 ± 7 yr; body mass index: 23.5 ± 2.5 kg · m-2) volunteered to participate in three trials: HIIE (10 x 60 s at 80% peak power output), MICE (50% peak power output of isocaloric duration), and a no-exercise control condition. Each exercise bout was performed at 18:00, and participants consumed a standardized evening meal at 20:00. Following an overnight fast, a 5-h mixed-macronutrient tolerance test was performed at 08:00. There were no significant differences in triglyceride incremental area under the curve between HIIE (192 ± 94 mmol. L-1 per 300 min), MICE (184 ± 111 mmol. L-1 per 300 min), and the no-exercise condition (175 ± 90 mmol. L-1 per 300 min) (P=0.46). There were no significant differences in incremental area under the curve for glucose (P=0.91) or insulin (P=0.59) between conditions. Upper-body MICE and HIIE performed in the evening do not influence PPL the following morning, in normotriglyceridemic individuals. Clinical Trials Registration: NCT04277091 Novelty: • Arm crank exercise has no effect on PPL when performed the evening prior to a mixed-macronutrient meal test • Upper-body sprint interval exercise should be investigated as a potential solution to reduce PPL.

Low adiponectin levels in primary hypertriglyceridemic male patients

Background and aims Adiponectin is an adipokine highly and specifically expressed by adipose cells with antiatherogenic and antiinflammatory activities. The aim of the present study was to evaluate plasma adiponectin concentration in patients with primary hypertriglyceridemia and its relationship with metabolic parameters. Methods and results Male patients with primary hypertriglyceridemia and without the metabolic syndrome ( n = 22) were compared with normotriglyceridemic individuals ( n = 25). Plasma adiponectin concentration was measured by standardised enzyme-linked immunosorbent assay. Body mass index, waist circumference, glucose, insulin and non-esterified fatty acid levels, lipoprotein profile, and CETP activity were evaluated. Adiponectin levels were significantly decreased in hypertriglyceridemic patients in comparison with normotriglyceridemic subjects (4292 ± 1717 vs. 6939 ± 3249 ng/ml, p < 0.005, respectively). Adiponectin was negatively associated with glucose ( r = − 0.44, p < 0.01), insulin ( r = − 0.37, p < 0.01), HOMA ( r = − 0.40, p < 0.01), triglycerides ( r = − 0.36, p < 0.01), VLDL-C ( r = − 0.34, p < 0.05), and CETP ( r = − 0.47, p < 0.001). Positive and significant correlations were observed with QUICKI ( r = 0.49, p < 0.001) and HDL-C ( r = 0.33, p < 0.05). In the multiple linear regression analysis, considering waist circumference, QUICKI, Log-triglycerides, HDL-C, and CETP as independent variables, Log-adiponectin showed a positive correlation with QUICKI, with an r 2 = 0.229 and p < 0.001. Therefore, the independent variable QUICKI explained the 23% of the variance in Log-adiponectin concentration. Conclusions We found low adiponectin levels in a population of primary hypertriglyceridemic men without the metabolic syndrome and an independent relationship between adiponectin concentration and insulin resistance. A reduction in insulin sensitivity and its impact on adiponectin concentration could be linked to high non-esterified fatty acid levels, increased triglyceride synthesis in the liver and impaired catabolism of triglyceride-rich lipoproteins.

Endothelial and leukocyte adhesion molecules in primary hypertriglyceridemia

Hypertriglyceridemia is known to be associated to functional impairment of the endothelium and, consequently, to higher risk of atherosclerosis. Nevertheless, some crucial steps in the development of the atherosclerotic plaque are still unknown in primary hypertriglyceridemia. The aim of the present study was to explore the expression of soluble and leukocyte-associated cell adhesion molecules in a group of patients with primary hypertriglyceridemia, both including (n=50) and excluding (n=24) subjects with metabolic syndrome, in comparison with control normotriglyceridemic individuals (n=30). Lipid profile, CETP activity, HDL and VLDL chemical composition were evaluated. Soluble (VCAM-1, ICAM-1 and E-selectin) and leukocyte cell adhesion molecules (CD18, CD49d and CD54) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively. Patients with primary hypertriglyceridemia as compared with control subjects showed significantly higher VCAM-1 (15.6±4.5ng/ml versus 13.9±3.8ng/ml, respectively; p<0.05) and ICAM-1 (16.9±3.1ng/ml versus 15.2±3.2ng/ml, respectively; p<0.05). Regarding leukocyte cell adhesion molecules, significant increases were also detected in monocyte CD18 (398±180 versus 332±136 arbitrary units, respectively; p<0.05) and CD54 (49±14 versus 42±12 arbitrary units, respectively; p<0.05), and lymphocyte CD18 (122±53 versus 101±33 arbitrary units, respectively; p<0.05). ICAM-1 plasma levels, as well as monocyte CD18 and CD54, and lymphocyte CD18 persisted elevated even if patients with metabolic syndrome were discarded among those with hypertriglyceridemia. The increase in circulating and leukocyte cell adhesion molecules in primary hypertriglyceridemic patients would highlight the inflammatory process which is a key event in atherogenesis.

Phenotypes, genotypes and response to statin therapy.

Response to statin treatment can vary widely from person to person as a result of inherited traits (genotype) and acquired characteristics such as obesity (phenotype). The aim of this review is to describe what is known about factors that determine a patient's response, and to offer a mechanism to explain how plasma triglyceride influences the nature and magnitude of lipid lowering on statin therapy. In normotriglyceridemic individuals statins have little impact on the concentration of large VLDL, but as basal plasma triglyceride rises there is an increasing tendency for large VLDL, chylomicrons, chylomicron remnants and small, dense LDL to fall on treatment. These phenotype-dependent effects are in contrast to the phenotype-independent actions on IDL and LDL. Recent studies have also revealed that the principal mechanism by which statins lower VLDL (and LDL) in hypertriglyceridemic individuals is by stimulation of lipoprotein clearance. Individuals with low HDL-cholesterol are increasingly treated with statins. The increase in this lipoprotein affects the subfraction distribution, with a specific increase in alpha1 HDL components. Polymorphism in the promoter for the ABCG8 gene has been linked to variations in response to statins; individuals with the rarer D19H genotype exhibit a greater reduction in LDL-cholesterol. Similarly, the magnitude of the statin-induced increase in HDL-cholesterol has been linked to a polymorphism in the promoter for apolipoprotein A1. Statins are administered to a wide range of individuals on an empirical basis. Investigation of the phenotype and genotype influences on treatment response will allow a more tailored use of these drugs.

Triglycerides are major determinants of cholesterol esterification/transfer and HDL remodeling in human plasma.

Lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are responsible for the esterification of cell-derived cholesterol and for the transfer of newly synthesized cholesteryl esters (CE) from HDL to apoB-containing lipoproteins in human plasma. LCAT and CETP are also crucial factors in HDL remodeling, a process by which HDL particles with a high capacity for cell cholesterol uptake are generated in plasma. In the present study, cholesterol esterification and transfer were evaluated in 60 patients with isolated hypercholesterolemia (HC, n = 20) and isolated (HTG, n = 20) or mixed hypertriglyceridemia (MHTG, n = 20) and in 20 normolipidemic healthy individuals (NL). Cholesterol esterification rate (CER) and net CE transfer rate (CETR) were measured in whole plasma. LCAT and CETP concentrations were determined by specific immunoassays. HDL remodeling was analyzed by monitoring changes in HDL particle size distribution during incubation of whole plasma at 37 degrees C. Mean CER and CETR were 48% and 73% higher, respectively, in hypertriglyceridemic (HTG + MHTG) versus normotriglyceridemic individuals. HDL remodeling was also significantly accelerated in plasma from hypertriglyceridemic patients. Strong positive correlations were found in the total sample between plasma and VLDL triglyceride levels and CER (r = .722 and r = .642, respectively), CETR (r = .510 and r = .491, respectively), and HDL remodeling (r = .625 and r = .620, respectively). No differences in plasma LCAT and CETP concentrations were found among the various groups except for a tendency toward higher CETP levels in hypercholesterolemic patients (+51% in MHTG and +20% in HC) versus control subjects (NL). By stepwise regression analysis, VLDL triglyceride level was the sole significant predictor of CER and CETR and contributed significantly together with baseline HDL particle distribution to HDL remodeling. These results indicate that plasma triglyceride level is a major factor in the regulation of cholesterol esterification/transfer and HDL remodeling in human plasma, whereas LCAT/CETP concentrations play a minor role in the modulation of reverse cholesterol transport.

Does an acute fat load promote elevations in plasma and serum viscosity of normotriglyceridemic individuals?

Does an acute fat load promote elevations in plasma and serum viscosity of normotriglyceridemic individuals?

Genetic markers in the apo AI-CIII-AIV gene cluster for combined hyperlipidemia, hypertriglyceridemia, and predisposition to atherosclerosis

The aim of the present study was to search for genetic determinants of combined hyperlipidemia and hypertriglyceridemia, and to evaluate whether such determinants might be associated with predisposition to atherosclerosis. Four DNA polymorphisms in the apo AI-CIII-AIV gene cluster (G to A mutation at position −75 basepairs in the apo AI promoter, XmnI, PstI and SstI) were studied in relation to combined hyperlipidemia, hypertriglyceridemia, lipoprotein levels, atherosclerosis and age in 221 Danish men. The frequency of the rare allele of the XmnI polymorphism, the X + allele, was higher in individuals below 55 years of age with combined hyperlipidemia than in individuals with normal lipid levels (0.31 vs. 0.14; P = 0.05). The rare allele of the SstI polymorphism, the S + allele, was more frequent in hyper-triglyceridemic individuals compared with normotriglyceridemic individuals (0.16 vs. 0.09; P < 0.05) and on analysis of variance the combined S − S + and S + S + genotypes were also associated with the highest triglyceride levels. Furthermore, the frequency of the S + allele decreased significantly as a function of age in nonatherosclerotic subjects (from 0.15 to 0.10 to 0.02 in 48-, 63- and 85-year-olds, respectively; 48- versus 85-year-olds, P = 0.03). These results suggest that genetic variation in the apo AICIIIAIV gene complex is associated with combined hyperlipidemia and hypertriglyceridemia and may have an impact on longevity and/or predisposition to atherosclerosis.

Properties of an apolipoprotein E-enriched fraction of triglyceride-rich lipoproteins isolated from human blood plasma with a monoclonal antibody to apolipoprotein B-100.

A monoclonal antibody to apolipoprotein (apo) B-100 (JI-H) with unique binding properties has been used to separate a population of triglyceride-rich lipoproteins from blood plasma of normotriglyceridemic individuals and patients with various forms of hypertriglyceridemia. This antibody fails to recognize an apoE-rich population of very low density lipoproteins (VLDL) containing apoB-100 as well as all triglyceride-rich lipoproteins containing apoB-48, but it binds other VLDL that contain apoE and almost all lipoproteins that contain apoB-100, but no apoE. The unbound triglyceride-rich lipoproteins separated by ultracentrifugation after separation from plasma by immunoaffinity chromatography contained 10-13% of the apoB of triglyceride-rich lipoproteins from three normotriglyceridemic individuals, 10-29% of that from five patients with endogenous hypertriglyceridemia, 40-48% of that from three patients with familial dysbetablipoproteinemia, and 65% of that from a patient with lipoprotein lipase deficiency. In all cases, the unbound triglyceride-rich lipoproteins contained more molecules of apoE and cholesteryl esters per particle than those that were bound to monoclonal antibody JI-H, and they were generally depleted of C apolipoproteins. These properties resemble those described for partially catabolized remnants of chylomicrons and VLDL. The affinity of the unbound lipoproteins for the low density lipoprotein (LDL) receptor varied widely, and closely resembled that of the total triglyceride-rich lipoproteins from individual subjects. Our results demonstrate that remnant-like chylomicrons and a population of remnant-like VLDL can be isolated and quantified in blood plasma obtained in the postabsorptive state from normotriglyceridemic and hypertriglyceridemic individuals alike.

Influence of serum triglycerides on the HDL pattern in normal subjects and patients with coronary artery disease

The distribution and structure of high density lipoprotein (HDL) subfractions were examined by rate zonal ultracentrifugation in 200 consecutive subjects, 86 of whom showed a stable hypertriglyceridemia, 22 with coronary artery disease. Among the remaining 114 normotriglyceridemic subjects, 75 were healthy and 39 had coronary disease. The serum levels of the HDL 2 subfraction were reduced by 22% in the 39 normotriglyceridemic coronary patients, and by 21% in the whole group of hypertriglyceridemic subjects. No difference in the HDL 3 levels was found in any of the studied group. There was a clear negative correlation between HDL 2 levels and triglyceridemia in the case of healthy people, not in coronary patients. By contrast, triglyceridemia was negatively correlated with the HDL 3flotation rate, both in healthy subjects and coronary patients at all triglyceride levels. Compositional data indicate that in hypertriglyceridemic subjects, HDL 2 levels are reduced because of an enhanced transfer-exchanged process between the enlarged VLDL pool and HDL; in contrast, in coronary patients, a defective maturation of the HDL 3 particle is the most likely underlying mechanism. Both in hypertriglyceridemic individuals, as well as in coronary patients, the HDL subfraction distribution is rather similar and drastically different from that of normotriglyceridemic healthy subjects. The mechanisms of the two conditions are probably different and, whereas a low concentration of HDL 2 is definitely a major risk factor for normotriglyceridemic individuals, in the case of hypertriglyceridemics other factors may come into play in the final determination of the coronary risk.

Relative contribution of triglyceride-rich lipoprotein particle size and number to plasma triglyceride concentration.

These studies were undertaken to determine whether differences in plasma triglyceride concentrations reflected differences in the number or in the size of the triglyceride-rich lipoprotein particles in the circulation. A population of 122 men and women, composed of normotriglyceridemic individuals and individuals with endogenous hypertriglyceridemia (plasma triglyceride concentration from 60 mg/dl to 1400 mg/dl), was studied by one of four independent experimental procedures. Rates of triglyceride production and particle (as reflected by apolipoprotein B) production were simultaneously determined. The data suggest that 71% of any increase in triglyceride production was due to an increase in the production of particles, and only 29% was due to an increase in the amount of triglyceride carried per particle. Direct measurement of the triglyceride-rich lipoprotein particle size by electron microscopy demonstrated that for a fivefold difference in triglyceride borne by the Sf 12-400 lipoproteins (from 100 mg to 500 mg triglyceride/dl plasma), the mean particle size rose by only 29%. Hence, 71% of this difference was due to an increase in particle number. The same results were obtained when triglyceride levels were related to the number of triglyceride-rich lipoproteins in the plasma. The number of particles for these studies was either estimated from apo B concentration or by calculations based on the chemical composition of ultracentrifugal subfractions. These studies have used four different approaches to show that changes of plasma triglyceride concentration primarily reflected a change in the number, not the size, of triglyceride-rich lipoprotein particles. Our studies also demonstrated that 75% to 80% of the triglyceride-rich lipoproteins in both normotriglyceridemic and hypertriglyceridemic subjects were in the Sf 12-60 or intermediate density lipoprotein subfraction.

Postprandial lipemia. A key for the conversion of high density lipoprotein2 into high density lipoprotein3 by hepatic lipase.

In this study, we have investigated the effects of alimentary lipemia in 15 normotriglyceridemic individuals on high density lipoproteins2 (HDL2) with respect to structure, composition, and substrate efficacy for hepatic lipase in vitro. In the study subjects, HDL2 levels ranged widely from 4.7 to 151.7 mg/dl plasma. HDL2 were isolated in the postabsorptive (pa) state and in the postprandial (pp) state, i.e., 7 h after ingestion of a standard fatty meal. In going from the pa state to the pp state, HDL2 exhibited higher flotation rates and lower densities due to a decreased proportion of protein (38.7----36.2%) and a higher abundance in phospholipid (32.5----34.9%). There was a variable increase in triglyceride at the expense of cholesteryl esters; this increase was correlated positively with the magnitude of pp lipemia (r = 0.69, P less than 0.01) and inversely with HDL2 levels (r = -0.72, P less than 0.01). Hdl2 fractions were incubated with human hepatic lipase in vitro. Product lipoproteins formed from lipolysis of pa-HDL2 and triglyceride-poorer pp-HDL2 were reduced in phospholipid content (by 25 and 50%, respectively) but remained in the size and density range of native HDL2. By contrast, a major fraction of triglyceride-richer pp-HDL2 was converted to particles with density, size, and apoprotein composition of native HDL3. Changes consistent with these findings in vitro were observed in vivo also, where 15 h postprandially, individuals with high-level lipemia showed a decrease in HDL2 and rise in HDL3, while those with lower-level lipemia did not. This study indicates that the magnitude of postprandial lipemia determines the proportion of triglyceride in pp-HDL2, which in turn determines whether or not HDL2 are converted to HDL3 by hepatic lipase action.

Human apolipoprotein C-I: Concentration in blood serum and lipoproteins

A radial immunodiffusion assay for apolipoprotein C-I in human serum and lipoproteins was developed and validated by comparison with analysis of these proteins in very-low-density and high-density lipoproteins by quantitative polyacrylamide gel electrophoresis. In normotriglyceridemic subjects, only about 10% of apoprotein C-I was in very-low-density lipoproteins; almost all of the remainder was in high-density lipoproteins. In subjects with widely varying serum triglyceride levels, apoprotein C-I comprised about 4% of the total apoprotein of the triglyceride-rich lipoproteins. In normotriglyceridemic subjects, apoprotein C-I comprised about 3% of the total apoprotein of high-density lipoproteins; this value was about twice as great in the high-density lipoproteins of density 1.063–1.125 g/ml as in those of density 1.125–1.21 g/ml. With increasing serum triglyceride level, the percentage of apoprotein C-I in triglyceride-rich lipoproteins increased and that in high-density lipoproteins fell progressively. Whereas apoprotein C-I comprised about 9% of the mass of the proteins of low molecular weight (<12,000) in very-low-density lipoproteins, it comprised about one-third of the mass of these proteins in high-density lipoproteins. As compared with the other major proteins of low molecular weight in human plasma lipoproteins (apoprotein C-II and apoprotein C-III), apoprotein C-I is therefore preferentially distributed in high-density lipoproteins. The average concentration of apoprotein C-I in serum of normotriglyceridemic individuals was 7 mg/dl; the concentration was not systematically increased in patients with primary hypertriglyceridemias.

Abnormal lipid composition of very low density lipoproteins in diagnosis of broad-beta disease (Type III hyperlipoproteinemia)

In an effort to define quantitative criteria for the diagnosis of broad-β disease (Type III hyperlipoproteinemia), the cholesterol and triglyceride contents of isolated very low density lipoproteins (VLDL, d < 1.006, Sf > 20) were analyzed in normal and hyper-lipoproteinemic subjects. The cholesterol/triglyceride ratio among the subjects with broad-β disease was 0.60 ± 0.11 (mean ± SD). This was significantly higher than the ratio among normal subjects (0.35 ± 0.08), subjects with familial hypercholesterolemia (Type IIa) (0.39 ± 0.05), endogenous lipemia (Type IV) (0.27 ± 0.06), or endogenous lipemia with chylomicrons (Type V) (0.25 ± 0.08). Among subjects who did not have broad-β disease, lower triglyceride levels were associated with a higher VLDL cholesterol/triglyceride ratio. Thus, among normo-triglyceridemic individuals ( triglyceride < 40 mg 100 ml ) several individual values for this ratio nearly overlapped with individual ratios from the broad-β group. However, no overlap in these ratios was observed between hyper-triglyceridemic subjects (Types IV and V) and those with broad-β disease. It is therefore proposed that a VLDL cholesterol/triglyceride ratio of > 0.42 (the upper limit of the range observed among subjects with endogenous lipemia) be considered diagnostic of broad-β disease in a hypertriglyceridemic individual.