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PubMed2001

Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is associated with the metabolism of lipid, glucose and energy. Beta-adrenergic receptors play an important role in the regulation of energy expenditure, in part, by stimulating lipid mobilization through lipolysis. METHODS: To assess whether it is common for the beta2-adrenergic receptor (B2AR) gene polymorphisms in codons 16 and 27 to play a role in the development of fatty liver, we investigated 251 unrelated healthy Japanese males who were drug-free and showed no signs of heavy drinking. RESULTS: The allelic frequency of B2AR gene mutation in codons 16 and 27 did not differ between obese subjects (BMI>25.0 kg/m(2), n=151) and non-obese subjects (BMI</=25.0 kg/m(2), n=100). The Gly16 homozygotes had a lower high-density lipoprotein cholesterol (HDL-C) level than the Arg16 homozygotes (1.50+/-0.4 vs. 1.32+/-0.3 mmol/l, p=0.014). However, no significant association with fatty liver was observed in the Gly16 allele frequency. The Gln27Glu27 heterozygotes showed higher concentrations of serum triglycerides (TG) than the Gln27Gln27 homozygotes (1.62+/-0.93 vs. 2.21+/-1.67 mmol/l, p=0.013). This correlation was also observed in all subjects regardless of weight classification. Univariate analysis indicated that subjects with the heterozygous Gln27Glu mutant alleles had a significantly higher prevalence of fatty liver vs. those without the mutation (Glu27 allele frequency, 0.07 vs. 0.12, p=0.047; odds ratio, 1.92; 95% confidence interval, 1.01-3.68). However, multivariate logistic regression models showed the prevalence of fatty liver to be significantly related to the homeostasis model assessment (HOMA) index, BMI, triglyceride and HDL-cholesterol. CONCLUSIONS: These results suggest that the amino-terminal polymorphisms of the beta2-adrenergic receptor gene in codon 27 were associated with hypertryglyceridemia and independent of obesity, and thereby could be involved in the molecular pathogenesis of fatty liver.

Adult↗
PubMed2002

Lipoprotein susceptibility to oxidation in the macromolecular fraction of plasma: relation to plasma lipids and oleate/linoleate ratio in comparison with whole plasma in hypertriglyceridemia.

BACKGROUND: Susceptibility of lipoprotein to oxidation is usually studied using purified lipoproteins. However, for large clinical studies or routine clinical assessment, a rapid less time-consuming method is desirable. Therefore, we studied copper-mediated oxidation of the macromolecule fraction of plasma in comparison with oxidation directly in whole unfractionated plasma in a group of hyperlipidemic individuals. METHODS: Lag phase rate (LR), propagation phase rate (PR), lag time (LT), and maximal extent of oxidation were determined for copper-mediated oxidation in plasma from 16 hyperlipidemic individuals. Oxidation parameters obtained for whole plasma (WP) and macromolecules were subjected to correlation analysis with plasma lipid concentrations and with the oleic acid/linoleic acid ratio (18:1/18:2) in phospholipids (PL), triglycerides (TG), and cholesterol esters (CE). RESULTS: Total cholesterol (TC) concentration was significantly correlated with lag rate (negative, p<0.05), lag time (positive, p<0.01), and with maximal extent of oxidation (positive, p<0.05) for plasma macromolecules (PM). Triglyceride concentration was not significantly correlated with lag rate, lag time, or propagation rate for plasma macromolecules. Triglyceride concentration was positively correlated with the maximal extent of oxidation (p<0.01) for plasma macromolecules. In the cholesterol ester fraction, the 18:1/18:2 ratio was significantly correlated (positive, p<0.05) with lag time. Phospholipid 18:1/18:2 ratio did not correlate with oxidative parameters. This ratio in triglycerides correlated better, but statistical significance was not obtained. Parameters obtained with whole plasma did not significantly correlate with lipid values. CONCLUSIONS: Oxidation parameters obtained for plasma macromolecules correlated with lipid parameters known to be associated with oxidative susceptibility of lipoproteins and were unaffected by soluble antioxidants found in whole plasma or serum. Therefore, plasma macromolecules were superior to whole plasma for assessing lipoprotein susceptibility to oxidation. This approach will facilitate larger clinical trials by saving the time and labor involved in lipoprotein isolation.

Chemical Fractionation↗
PubMed2002

Hypertriglyceridemia is associated with an elevated blood viscosity Rosenson: triglycerides and blood viscosity.

Elevated blood viscosity is a predictor of cardiovascular disease. The major determinants of blood viscosity are hematocrit and plasma viscosity. Plasma triglycerides elevate plasma viscosity; however, the contribution of plasma triglycerides to blood viscosity after adjustment for other major covariates has not been reported. This cross-sectional study of 257 adult subjects evaluated the associations between fasting plasma lipids, fibrinogen, total serum protein, hematocrit and blood viscosity. Blood viscosity was measured at 37 degrees C with a coaxial cylinder microviscometer at shear rates of 100 and 1 s(-1). Blood viscosity values are reported both as uncorrected measurements and measurements corrected to a hematocrit of 45% by a regression equation. Uncorrected blood viscosity at a shear rate of 100 s(-1) was significantly associated with triglycerides, fibrinogen, high density lipoprotein (HDL) cholesterol, total serum protein, and hematocrit using stepwise multivariate regression analysis. When corrected blood viscosity at 100 s(-1) was the dependent variable, there were statistically significant associations with triglycerides, HDL cholesterol, and total serum protein. Corrected blood viscosity at 1 s(-1) was significantly associated with triglycerides, fibrinogen, total serum protein, and an indicator variable for diabetes mellitus. This study supports an additional mechanism whereby triglycerides may contribute to cardiovascular risk.

Adult↗
PubMed2000

Management of selected lipid abnormalities. Hypertriglyceridemia, low HDL cholesterol, lipoprotein(a), in thyroid and renal diseases, and post-transplantation.

Although the focus in treating lipid disorders is on reducing LDL cholesterol levels, triglycerides, HDL cholesterol, and Lp(a) are all independent risk factors that can be used clinically to assess cardiovascular risk. Decisions to initiate drug therapy for LDL cholesterol reduction may be influenced by levels of these other lipoprotein fractions. Data supporting intervention to modify these factors is less abundant than for LDL cholesterol reduction, but in certain circumstances drug therapy targeted at triglycerides or HDL cholesterol may be appropriate. Patients with nephrotic syndrome and end-stage renal disease are at particularly high risk for the development of cardiovascular disease and should be treated aggressively for lipid disorders. Finally, solid organ transplant recipients are almost always hyperlipidemic, and appropriate therapy could reduce cardiovascular events.

Adult↗
PubMed2001

Changes in hemostasis during treatment of hypertriglyceridemia with a diet rich in monounsaturated and n-3 polyunsaturated fatty acids in comparison with a low-fat diet.

High levels of fibrinogen, factor (F) VIIc, plasminogen activator inhibitor-1 (PAI-1), and plasma viscosity are associated with an increased coronary risk. As positive correlations of these parameters with triglycerides have been shown, the increased coronary risk associated with high levels of triglycerides may be assumed to be due to alterations within the hemostatic system. To reduce the coronary risk to which hypertriglyceridemic patients are exposed, dietary treatment is recommended; the optimal composition of such a diet is, however, a matter of debate. With regard to the effects on hemostasis, we compared in a sequential approach two diets for treatment of 25 nonobese male patients (age, mean+/-S.D., 40.4+/-8.7 years) with fasting triglycerides >2.3 mmol/l. The first diet (high fat) was rich in monounsaturated fatty acids (MUFA) and marine n-3 polyunsaturated fatty acids (PUFA), whereas the second diet (low-fat) was rich in complex carbohydrates and dietary fiber. The high-fat diet induced a significant lowering of FIIc, FIXc, FXc, FVIIc, FVIIa, FXIIa, PAI-1, plasma viscosity, and platelet activity, but led to an increase in fibrinogen, whereas the low-fat diet lowered FXIIc values and induced a nonsignificant decrease in fibrinogen. Probands on this diet had a slightly higher FVIIa and platelet activity than those on the high-fat diet. However, as all changes appeared to be within the normal range of each hemostatic parameter, it remains to be clarified whether the likely beneficial effects of the high-fat diet on most hemostatic factors are outweighed by the small increase in fibrinogen levels.

Adult↗
PubMed1999

Improving effects of the extracts from Eugenia uniflora on hyperglycemia and hypertriglyceridemia in mice.

EtOH (70%) extracts from the leaves of Eugenia uniflora were separated into six fractions with different polarity and molecular size, i.e. NP-1-NP-6. In an oral glucose tolerance test, NP-1 and 4 inhibited the increase in plasma glucose level. However, in an intraperitoneal glucose tolerance test, such an inhibitory effect was not seen. Thus, the effects of NP-1 and 4 were apparently due to the inhibition of glucose absorption from the intestine. In a sucrose tolerance test, all fractions inhibited the increase in plasma glucose level. In an oral corn oil tolerance test, NP-3 and 4 showed an inhibitory effect on the increase in plasma triglycerides level. On the other hand, NP-3, 4, 5 and 6 inhibited maltase and sucrase activities and all fractions except for NP-1 showed an inhibitory effect on lipase activity dose-dependently. The inhibition of the increase in plasma glucose level by NP-3, 4, 5 and 6 in the oral sucrose tolerance test and the inhibition of the increase in plasma triglycerides by NP-3 and 4 in the oral corn oil tolerance test were apparently due to the inhibition of the decomposition of carbohydrates and fats in the intestine, respectively.

Animals↗
PubMed2003

Management of selected lipid abnormalities: hypertriglyceridemia, isolated low HDL-cholesterol, lipoprotein(a), and lipid abnormalities in renal diseases and following solid organ transplantation.

Although the focus in treating lipid disorders is on reducing LDL-C levels, additional lipid-related independent risk factors, such as TG, HDL-C, and Lp(a) levels, should be used clinically to assess cardiovascular risk. Decisions to initiate drug therapy for LDL-C reduction may be influenced by levels of these other lipoprotein fractions. Data supporting intervention to modify these factors are less abundant than for LDL-C reduction, but in certain circumstances. drug therapy targeted at TGs or HDL-C may be appropriate. Patients who have nephrotic syndrome and end-stage renal disease are at particularly high risk for the development of CVD and should be treated aggressively for their lipid disorders. Finally, solid organ transplant recipients are almost always hyperlipidemic and appropriate therapy could reduce cardiovascular events.

Cardiovascular Diseases↗