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A mutation of the beta 3-adrenergic receptor is associated with visceral obesity but decreased serum triglyceride.

The Trp64Arg mutation of the beta 3-adrenergic receptor (beta 3AR) is prevalent in several ethnic groups and is associated with weight gain, and some features of syndrome X such as insulin resistance and dyslipidaemia. Nevertheless, it is not known at present whether this mutation is associated with visceral obesity, which is an important risk factor for the development of hypertension, dyslipidaemia, insulin resistance, non-insulin-dependent diabetes mellitus, and atherosclerosis. To investigate whether this mutation may contribute to visceral obesity, we studied the relationships between beta 3AR genotypes and clinical phenotypes. The Trp64Arg allele of beta 3AR was examined in 278 Japanese men with respect to variables relating to visceral obesity assessed by computerised tomography. To detect the Trp64Arg mutation, polymerase chain reaction-restriction fragment length polymorphism analysis using Bst NI digestion was performed. This mutation was more frequently observed in subjects with higher body mass index (BMI) (p = 0.02). Moreover, in 120 subjects with a moderate degree of obesity (22 < or = BMI < 26.4 kg/m2), the mutation (homozygotes and heterozygotes) was associated with visceral obesity (higher ratio of visceral to subcutaneous fat area; V/S) (p = 0.03). Furthermore, the Trp64Arg allele was more frequent in subjects with lower serum triglyceride levels (p = 0.02) and the Trp64Arg homozygotes, but not heterozygotes, exhibited lower triglyceride levels. Thus, this mutation appears to be associated with visceral obesity but with lower serum triglyceride. It is suggested that those with the mutation may describe a subset of subjects characterized by decreased lipolysis in visceral adipose tissue.

Adult↗

Triglycerides, apo C3 and Lp B:C3 and cardiovascular risk in type II diabetes.

AIMS/HYPOTHESIS: Cardiovascular complications and particularly coronary heart disease are the main causes of morbidity and mortality in Type II (non-insulin-dependent) diabetes mellitus. Some studies have shown that hypertriglyceridaemia in diabetes is an independent cardiovascular risk factor. In the ECTIM study high apolipoprotein C3 and lipoprotein B:C3 concentrations (lipoparticles playing a role in triglyceride metabolism) were associated with myocardial infarction in non-diabetic subjects. METHODS: We studied the relations between macroangiopathy and different cardiovascular risk factors and lipid variables in 188 Type II diabetic subjects. RESULTS: Multivariate analysis showed that triglycerides, apo C3 and Lp B:C3, sex, duration of diabetes, microalbuminuria and age were independently associated with macroangiopathy. The study group was divided into quartiles according to apo C3 and Lp B:C3 concentrations: the prevalence of macroangiopathy and coronary heart disease were increased in upper quartiles. CONCLUSION/INTERPRETATION: Triglycerides apo C3 and Lp B:C3 were independent cardiovascular risk markers in our group of Type II diabetic patients.

Apolipoprotein C-III↗

Variable effects of the APOC3-482C > T variant on insulin, glucose and triglyceride concentrations in different ethnic groups.

AIMS/HYPOTHESIS: The apolipoprotein C3-482C> T variant modulates insulin and glucose concentrations after an oral glucose tolerance test (OGTT) in young healthy white men. We evaluated the effect of this variant in different ethnic groups with different rates of Type II (non-insulin-dependent) diabetes mellitus and coronary heart disease. METHODS: We investigated the -482C > T in a population-based cross-sectional study of white subjects (n = 462), South Asians (n = 442) and subjects of West African and Afro-Caribbean origin (n = 462), whose OGTT and fasting plasma triglyceride concentrations had been measured. RESULTS: The -482T allele frequency differed between the three groups: 0.25 (95 % CI 0.22-0.28) in white subjects, 0.44 (0.41-0.47) in South Asians and 0.71 (0.68-0.74) in black subjects (p < 0.0001). A positive association was found between body mass index and genotype in black women (p = 0.009) and in black men (p = 0.056) but not in white subjects or South Asians. Associations between -482C > T and fasting insulin were found in white subjects, where -482T allele carriers had higher concentrations (adjusted for age and sex, p = 0.007, also including smoking and body mass index, p = 0.038). Higher triglyceride concentrations (p = 0.004 and p = 0.007 in the two models) but not glucose concentrations were also associated with -482C > T. In black subjects, decreased fasting insulin (p = 0.04) and fasting glucose (p = 0.004) were associated with -482C > T. No relation was observed between genotype and any post-load measured. CONCLUSIONS/INTERPRETATION. Allele frequencies of the -482C > T and associations with insulin, glucose and triglyceride concentrations vary considerably among ethnic groups. Although the results are consistent among white subjects across different studies, the associations among black subjects and South Asians differ.

Adult↗

Positive associations of bone mineral density with body mass index, physical activity, and blood triglyceride level in men over 70 years old: a TCVGHAGE study.

It is known that osteoporosis decreases physical function in older males. However, the role of metabolic parameters and physical activity influencing older men's bone status remains unclear. Thus, this study was designed to evaluate calcaneus bone mass by ultrasonic screening and the associated physical and metabolic functions in older men. This was a cross-sectional study. Three hundred sixty-eight older men (average age, 78.8 years) living in a veterans' home were enrolled. We measured body height and weight, waist and hip circumference, body fat, lean body mass, blood pressure, 6-min walking distance, complete blood count, and blood biochemical profile. Broadband ultrasound attenuation (BUA) and T-score were recorded using Soundscan quantitative ultrasound over the right calcaneus. The range of calcaneus BUA was 27.3-134.0; T-score was from -4.78 to 3.43. Of the total participants, 36.4% were osteopenic (-2.5 < T-score < -1.0) and 16.3% were osteoporotic (T-score <or= -2.5). BUA correlated with weight, body mass index (BMI), waist circumference, hip circumference, body fat, lean body mass, serum triglycerides, high-density lipoprotein-cholesterol, albumin, prealbumin, fasting and PC-2h blood insulin, red blood cell count, hemoglobin concentration, and 6-min walking distance. Multiple regression stepwise analysis revealed that only BMI, distance of 6-min walking, and blood triglyceride level were independently and positively associated with the values of BUA. Calcaneus bone mass is significantly and positively associated with BMI, blood triglycerides, and 6-min walking distance in older men.

Aged↗

Stimulation of triglyceride-rich lipoprotein secretion by polysorbate 80: in vitro and in vivo correlation using Caco-2 cells and a cannulated rat intestinal lymphatic model.

PURPOSE: To assess the effects of polysorbates 80 and 60 on intestinal lipoprotein processing in vitro, using Caco-2 cells, and to compare the results with those obtained using an in vivo intestinal lymphatic cannulated rat model. METHODS: Caco-2 monolayers were used to monitor changes in lipoprotein secretion following exposure to excipients. In vivo data was obtained by monitoring intestinal lymphatic triglyceride levels following intraduodenal administration of the excipient to an anesthetised mesenteric lymph cannulated rat. RESULTS: Caco-2 cells digested the polysorbate 80 to liberate oleic acid, which was used by the cells to enhance basolateral secretion of triglyceride-rich lipoproteins including chylomicrons. This response was not seen with polysorbate 60. Polysorbate 80 elicited a similar response in vivo in the rat model, stimulating enhanced triglyceride secretion in mesenteric lymph. Inhibition of lipoprotein secretion by Cremophor EL in Caco-2 cells was reversed by co-administration with polysorbate 80. CONCLUSIONS: Polysorbate 80 promoted chylomicron secretion in Caco-2 cells and counteracted the inhibitory effects of other surfactants. These properties, in tandem with its P-gp inhibitory activity, make polysorbate 80 an ideal excipient for lymphotrophic vehicles. The ability to predict the in vivo response to Polysorbate 80 implies that the Caco-2 model is useful for studying absorption mechanisms from oral lipid-based formulations.

Animals↗

Water-soluble organosulfur compounds of garlic inhibit fatty acid and triglyceride syntheses in cultured rat hepatocytes.

The putative hypolipidemic effect of garlic remains controversial. To gain further insight into the effect of garlic on lipid metabolism, the present study determined the inhibitory effects of water-soluble organosulfur compounds present in garlic on triglyceride (TG) and fatty acid synthesis in cultured rat hepatocytes. When incubated at 0.05 to 4.0 mmol/L with cultured hepatocytes, S-allyl cysteine (SAC) and S-propyl cysteine (SPC) decreased [2-14C]acetate incorporation into triglyceride in a concentration-dependent fashion achieving a maximal inhibition at 4.0 mmol/L of 43 and 51%, respectively. The rate of [2-14C]acetate incorporation into phosphlipids was depressed to a similar extent by SAC and SPC. SPC, SAC, S-ethyl cysteine (SEC), and gamma-glutamyl-S-methyl cysteine decreased [2-14C]acetate incorporation into fatty acid synthesis by 81, 59, 35, and 40%, respectively, at 2.0-4.0 mmol/L concentrations. Alliin, gamma-glutamyl-S-allyl cysteine, gamma-glutamyl-S-propyl cysteine S-allyl-N-acetyl cysteine, S-allylsulfonyl alanine, and S-methyl cysteine had no effect on fatty acid synthesis. The activities of lipogenic enzymes, fatty acid synthase (FAS), and glucose-6-phosphate dehydrogenase (G6PDH) were measured in cultured hepatocytes treated with the inhibitors. The activity of FAS in cells treated with 4.0 mmol/L SAC and SPC, respectively, was 32 and 27% lower than that of nontreated cells. Neither SAC nor SPC affected G6PDH activity. The results indicate that SAC, SEC, and SPC inhibit lipid biosynthesis in cultured rat hepatocytes, and further suggest that these S-alk(en)yl cysteines of garlic impair triglyceride synthesis in part due to decreased de novo fatty acid synthesis resulting from inhibition on FAS. Whether tissue concentrations of active garlic components can achieve levels required to inhibit TG synthesis in vivo warrants further investigation.

Acetates↗

Studies on effects of dietary fatty acids as related to their position on triglycerides.

This article reviews published literature on how the stereospecific structure of dietary triglycerides may affect lipid metabolism in humans. Animal studies have shown enhanced absorption of fatty acids in the sn-2 position of dietary triglycerides. Increasing the level of the saturated fatty acid palmitic acid in the sn-2 position (e.g., by interesterification of the fat to randomize the positions of the fatty acids along the glycerol backbone) has been shown in rabbits to increase the atherogenic potential of the fat without impacting levels of blood lipids and lipoproteins. In contrast, enhancing the level of stearic acid in the sn-2 position has not been found to affect either atherogenic potential or levels of blood lipids and lipoproteins in rabbits. Fatty acids other than palmitic and stearic have not been studied systematically with respect to possible positional effects. A limited number of human studies have shown no significant effects of interesterified fats on blood lipid parameters. However, it is unknown whether modifying the stereospecific structure of dietary triglycerides would affect atherogenicity or other long-term health conditions in humans. It is possible that incorporation of palmitic acid into the sn-2 position of milk fat is beneficial to the human infant (as a source of energy for growth and development) but not to human adults. Additional research is needed to determine whether processes like interesterification, which can be used to alter physical parameters of dietary fats (e.g., melting characteristics), may result in favorable or unfavorable long-term effects in humans.

Absorption↗

Effects of the glycemic index of foods on serum concentrations of high-density lipoprotein cholesterol and triglycerides.

The role of carbohydrates in cardiovascular disease prevention has garnered increasing attention due to accumulating evidence showing deleterious effects of low-fat, high-carbohydrate diets on serum triglycerides and high-density lipoprotein (HDL) cholesterol. Researchers argue that classifying carbohydrates based on their capacity for increasing blood glucose (termed the glycemic index ) is a useful tool for elucidating the effects of carbohydrate-rich foods on glucose and lipid metabolism. Several epidemiologic reports show that lower dietary GI is associated with lower serum triglycerides and higher HDL cholesterol. Results from intervention studies show that substituting low-GI for high-GI foods in a low-fat, high- carbohydrate diet lowers serum triglycerides by 15% to 25%. The available evidence to date suggests that the glycemic index of foods will be an important factor in future dietary prevention research.

Cholesterol, HDL↗

Targeting triglycerides as prognostic indicators and determining lowest values for patient benefit.

A number of reports demonstrate the importance of serum triglyceride values in predicting the clinical onset of vascular disease. However, adjustment for measurements highly correlated with triglyceride (TG) levels, such as history of diabetes, body mass index, and high-density lipoprotein cholesterol (HDL-C), lessen if not remove the TG contribution to outcomes. More recently, improved analytic approaches have more persuasively implicated triglycerides as independently relevant to the onset of cardiovascular disease. Elevated TG values are the consequence of larger TG-rich particles, including very low density lipoprotein and atherogenic intermediate particles, which are in turn associated with dense low-density lipoprotein. It has been observed that a reduction in TG concentrations often proceeds in parallel with improved clinical outcomes; however, direct correlation between the two has been elusive. This has been demonstrated in multiple pharmacologic trials. However, an improvement in these relationships has been observed when TG-correlated measurements of intermediate particles, low-density lipoprotein density, and HDL-C have been made. National guidelines for cholesterol treatment have now incorporated a TG greater than 200 mg/dL as a secondary treatment trigger, which targets apolipoprotein B-related particles, represented by non-HDL-C (total cholesterol minus HDL-C), as the suggested goal of therapy.

Cardiovascular Diseases↗

Epidemiology of triglycerides: a view from Framingham.

New analyses from the Framingham Heart Study are presented showing that men and women who have high triglyceride levels (> 1.7 mmol/liter) and a low high-density lipoprotein (HDL) level (< 1.03 mmol/liter) run a significantly higher rate of coronary artery disease and can be identified, and that this risk group (high triglyceride-low HDL) is, independently of the major risk factors (including low HDL), related to occurrence of coronary artery disease. Further, this trait appears to be common in our society, producing twice as many cases of coronary artery disease during the 14 years of the Framingham study as the next highest disease-producing lipid abnormality. This trait of high triglyceride-low HDL is associated in the medical literature with increased insulin resistance, higher blood sugars (within the normal range), higher uric acid levels, hypertension, and centrally mediated obesity. Because total cholesterol in people with these traits may be less than or just slightly greater than 5.2 mmol/liter, they are missed or neglected by most cholesterol screening programs.

Adult↗

Role of triglycerides in coronary artery disease: lessons from the Prospective Cardiovascular Münster Study.

The incidence of atherosclerotic coronary artery disease (CAD) was assessed in 4,576 male participants of the Prospective Cardiovascular Münster (PROCAM) study, aged 40-64 years, over a 4-year follow-up period. In this time, 122 study participants developed atherosclerotic CAD (89 definite nonfatal myocardial infarctions and 33 definite atherosclerotic CAD deaths). Univariate analysis revealed a significant association between the incidence of atherosclerotic CAD, and high-density lipoprotein (HDL) cholesterol (p < 0.001) and triglyceride (p < 0.01) levels. The relation to HDL cholesterol remained after adjustment for other risk factors. By contrast, the relation between the incidence of atherosclerotic CAD and triglycerides disappeared if, in a multivariate analysis by means of a multiple logistic function, cholesterol or HDL cholesterol was taken into account. However, the data suggested that hypertriglyceridemia is a powerful additional coronary risk factor, when excessive triglycerides coincide with a high ratio (> 5.0) of plasma low-density lipoprotein (LDL) cholesterol to HDL cholesterol. Even though the prevalence of this subgroup was only 3.7%, it included a quarter of all atherosclerotic CAD events observed.

Adolescent↗

Diet-induced changes in serum transaminase and triglyceride levels in healthy adult men. Role of sucrose and excess calories.

Serum transaminase levels were measured as part of a study on the physiologic control of food intake. Twenty-one men, 15 nonobese and six obese, were housed on a metabolic ward for 30 days where they received ad libitum a baseline diet of conventional foods containing 25 to 30 percent of total calories as sucrose for 18 days and a calorically diluted diet containing less than 10 percent sucrose for 12 days. Serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) levels rose significantly when subjects consumed the baseline diet and returned to their original levels on the calorically diluted aspartame-sweetened diet. Markedly abnormal transaminase levels developed in two subjects on the baseline diet and they had to be discharged from the study. Correlations between various components of the diet and enzyme changes suggested that both surplus calories and a high sucrose intake played a role in the elevation of enzyme levels. Serum triglyceride levels also showed a significant reduction when the subjects were switched from the baseline to the calorically diluted diet. In a second study designed to test systematically the role of sucrose on SGPT and SGOT levels and on serum triglyceride levels, six nonobese subjects received a carefully controlled liquid diet, relatively high in linoleic acid content, containing 50 percent of total calories as either sucrose or maltose. In comparison with the first study, sucrose had a smaller but still significant effect on the levels of both enzymes, but there was no significant effect on triglyceride levels.

Adult↗

Plasma glucose, cholesterol, triglyceride, and glycerol concentrations in the postmature rabbit.

Plasma cholesterol, triglycerides, glycerol, and glucose concentrations were measured in term and postmature rabbits. The data show that the term and postmature mothers have significantly higher glycemia than their fetuses. However, triglyceride and cholesterol concentrations are lower in the postmature mother than in her fetus. Postmature fetuses are characterized by very high plasma triglyceride and cholesterol concentrations. The results demonstrate that postmaturity is accompanied by maternal and fetal lipid metabolic changes related to a decrease in the transfer of maternal fatty acids through the placenta and to a diminution in fetal liver glucose utilization. The postmature fetus is then in a relative state of fasting and must rely on its own supply of fuel (glycogen and lipids) to provide cells for growth and survival. The maternal metabolic changes can possibly be explained by a decreased utilization of maternal substrates by the fetus, the placenta becoming insufficient. The close interrelationship of fetal and maternal lipid metabolism with the activity of the placenta suggests that an accurate knowledge of the metabolic changes taking place in the fetus during alteration of the maternal environment is indispensable to the understanding of the short- and long-term effects of maternal disease on the fetus.

Animals↗

A fluorometric method for the determination of triglycerides in nanomolar quantities.

A fluorometric assay for triglycerides in nanomole quantities is described. Glycerol is liberated from triglycerides with lipase from Chromobacter viscosum, then converted by glycerol kinase to glycerol-3-phosphate, which is oxidized by glycerol-3-phosphate oxidase, producing H2O2. The H2O2 ultimately forms a peroxidase-catalyzed fluorogen with p-hydroxyphenylacetic acid. The excitation and emission wavelengths of the fluorogen are 325 and 415 nm, respectively. The assay is linear in the range 0.05-35 nmol of triglycerides using triolein as standard.

Chromatography, Liquid↗

A rapid quantitative determination of triglycerides by means of thin-layer chromatography.

A quantitative chromatographic method for determining triglycerides in serum is described. The serum is applied directly to a thin-layer plate and after partition with one developing solvent the fractions are charred with 10% sulphuric acid. Charring takes 20 minutes. The concentration of triglycerides is measured against a triolein standard, which in itself is corrected for having too many double bonds by scanning the charring of the triglyceride fraction with a "flying spot"-scanner or a slitscanner. The results are compared with other methods of determination.

Chromatography, Thin Layer↗

Determination of serum triglycerides by mass fragmentography.

A mass fragmentographic reference method for determination of serum triglycerides is described. A fixed amount of a mixture of [1,1,2,3,3-2H5]glycerol tripalmitate and [1,1,2,3,3-2H5]glycerol trioleate (500 nmol) is added to a fixed amount of serum (250 mul) and extracted with chloroform/methanol (2 : 1, v/v). The triglycerides are isolated by means of thin-layer chromatography. The glycerol obtained after acid hydrolysis is converted into the tri-trimethylsilyl derivative and the amount of unlabeled glycerol is determined from the ratio between the recordings at m/e 218 m/e 222, obtained after analysis with a gas chromatograph-mass spectrometer equipped with an MID (multiple ion detector). The two ions correspond to the peak at M--90 and M--91 in the mass spectrum of the tri-trimethylsilyl derivative of unlabeled and (1,1,2,3,3-2H5)-labeled glycerol. The relative standard deviation of the method in the range 0.4--5.8 mmol/l was 2.4%. A fully enzymatic routine method for determination triglycerides was compared with the mass fragmentographic reference method. There was a good correlation between the two methods (r = 0.995) and the regression coefficient was 1.19.

Gas Chromatography-Mass Spectrometry↗

A simple colorimetric method for determination of serum triglycerides with lipoprotein lipase and glycerol dehydrogenase.

A simplified enzymic procedure to determine accurately serum triglycerides is described. Serum triglycerides are hydrolyzed completely to free fatty acids and glycerol by lipoprotein lipase from Pseudomonas fluorescens. The released glycerol is oxidized with glycerol dehydrogenase from Erwinia aroideae in the presence of NAD+, were the reduction of the enzyme-linked NAD+ is coupled to the reduction of nitro blue tetrazolium as a chromogenic indicator with phenazine methosulfate serving as an intermediate electron carrier of NADH. The absorbance at 570 nm is measured. The method requies only 20 microliter of serum and a 10-min incubation and is rapid and simple. The present method offers the measurement of a high concentration of triglyceride up to 1000 mg/dl serum. The results obtained by the present method show good correlation with those obtained by the glycerol kinase method (correlation coefficient, 0.989) or the acetylacetone method (correlation coefficient, 0.979). These results suggest that the proposed method will be utilized as a method or routine clinical test.

Colorimetry↗

Preparation of reference sera with desired levels of cholesterol and triglyceride.

Simple methods for isolating cholesterol-rich protein fraction from human serum and triglyceride-rich fraction from hen egg yolk are presented. The isolated fractions are combined separately with small volumes of human serum in order to stabilize concentrated cholesterol and triglyceride. Precalculated volumes of concentrates are added to human serum in order to prepare reference sera with desired levels of cholesterol or triglyceride, or both. The reference sera resemble human serum in appearance, composition, and stability. Properties of preparations are discussed and stability of reference sera is illustrated.

Blood Proteins↗