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PubMed2001

Symmetrical cationic triglycerides: an efficient synthesis and application to gene transfer.

Some cationic triglycerides 1Aa-1Cb which have a symmetrical structure were effectively synthesized and formulated into cationic liposomes with the co-lipid dioleoylphosphatidylethanolamine (DOPE) and/or dilauroylphosphatidylcholine (DLPC). The plasmid encoding a luciferase was delivered into CHO cells by using these cationic liposomes. Our symmetrical cationic triglycerides showed high transfection activity when DOPE was used as a co-lipid. Among the symmetrical cationic triglycerides synthesized here, 1Ab and 1Ac, which have an oleoyl group at the 1- and 3-position in the glycerol backbone and also have a relatively long linker connecting the 2-hydroxy group in glycerol with the quaternary ammonium head group, were found to be the most suitable for gene delivery into cells. The transfection activity of the symmetrical cationic triglyceride 1Ab was comparable with that of its asymmetrical congener 6 and several times higher than that of Lipofectin.

Animals↗
PubMed2003

Congenital generalized lipodystrophy: significance of triglyceride biosynthetic pathways.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by marked lack of body fat since birth, which results in striking muscular appearance. Patients develop extreme insulin resistance and its complications, such as diabetes, hyperlipidemia and fatty liver. Mutations in the BSCL2 (which encodes seipin, a protein of unknown function) and AGPAT2 (which encodes 1-acylglycerol-3-phosphate O-acyltransferase 2) genes have been reported in patients with CGL. AGPAT2 is a key enzyme involved in triglyceride and phospholipid biosynthesis and, thus, the discovery of AGPAT2 mutations has heightened interest in the biochemical pathways of triglyceride synthesis and their implications in human physiology and in the pathophysiology of obesity, lipodystrophies and other adipose tissue disorders. All enzymes involved in triglyceride synthesis, including AGPAT, have several known isoforms encoded by different genes. Assuming different substrate specificities of these enzymes, the human body might have many forms of triglycerides and phospholipids. Here, we discuss the significance of these in energy storage, in addition to the normal functioning of cell membranes.

Animals↗
PubMed2000

DGAT and triglyceride synthesis: a new target for obesity treatment?

Because triglycerides are considered essential for survival and their synthesis has been thought to occur through a single mechanism, inhibiting triglyceride synthesis has been largely unexplored as a possible target for obesity treatment. However, recent studies indicate that mice lacking acyl CoA:diacylglycerol acyltransferase (DGAT), a key enzyme in triglyceride synthesis, are viable and resistant to diet-induced obesity. Unexpectedly, this resistance is caused by a mechanism involving increased energy expenditure. These findings suggest that inhibiting specific components of triglyceride synthesis, such as DGAT, is feasible and may represent a novel approach to treating obesity.

Acyltransferases↗
PubMedDate not supplied

Low-density lipoprotein particle size decreases during normal pregnancy in association with triglyceride increases.

OBJECTIVE: To characterize the changes in low-density lipoprotein (LDL) peak particle diameter (diameter of the predominant LDL subclass) in relation to changes in serum triglyceride concentration during successive stages of normal gestation and postpartum. METHODS: Nonfasting venous blood was obtained longitudinally during and after uncomplicated primiparous pregnancy from 10 nonsmoking women with no history of metabolic disorders. Plasma LDL diameter was determined by nondenaturing polyacrylamide gel electrophoresis. Serum concentrations of total cholesterol, triglyceride, apolipoprotein B, apolipoprotein A-I, and LDL-cholesterol were measured. Gestational changes were analyzed by one-way repeated-measures analysis of variance and the paired multiple comparison Student-Newman-Keuls test. Pearson coefficients were computed for correlation of serum lipids and LDL diameter. RESULTS: Low-density lipoprotein diameter decreased progressively with advancing gestation, evident by 16-20 weeks relative to 5-12 weeks. Seven of 10 cases were subclass pattern B (diameter less than 255 A) by term, indicating that small, dense particles predominated. The average diameter decrease from early to late gestation was 13 A. All subjects reverted to subclass pattern A (diameter 255 A or more) by 6-12 weeks postpartum, indicating prevalence of large, buoyant LDL. Low-density lipoprotein diameter correlated inversely with concentrations of serum triglyceride (r = -.61, P < .0001), apo B (r = -.66, P < .0001), cholesterol (r = -.53, P < .001), LDL cholesterol (r = -.45, P < .005), and apo A-I (r = -.39, P < .02). CONCLUSION: Gestational triglyceride increases are accompanied by progressive decreases in LDL diameter in a majority of cases. These changes undergo reversal postpartum and therefore are transient. Small, dense LDL particles have a number of properties capable of altering vascular function. However, the consequences of the gestational LDL size decrease for maternal and fetal metabolism remain unknown.

Apolipoprotein A-I↗
PubMed1996

Computed tomography scanning of Morris hepatomas with liver-specific polyiodinated triglycerides.

RATIONALE AND OBJECTIVES: We compared the computed tomography (CT) scanning characteristics of a polyiodinated triglyceride analog with those of a urographic agent to distinguish Morris-7777 hepatoma (MH) cells from normal hepatocytes in rats. METHODS: Eighteen Buffalo rats were laparotomized and MH cells injected directly into the hepatic parenchyma or introduced via the portal vein to produce, respectively, focal or diffuse lesions in the liver. Baseline CT scans were obtained 21 days after implantation and prior to intravenous administration of either the polyiodinated triglyceride (45-100 mg I/kg) or the nonionic contrast agent, iohexol (560 mg I/kg). Images were obtained at 0-3 hr and 24 hr. Gross pathologic inspection was performed to validate the imaging results. RESULTS: Hepatomas were nearly isodense with normal liver parenchyma in many of the animals, rendering lesion detection difficult with no contrast agent. The bolus administration of iohexol improved lesion detection in many cases. Lesion conspicuity, however, was significantly improved with the polyiodinated triglyceride at less than one eighth the dose of iohexol. CONCLUSION: Because of their biochemical nature, polyiodinated triglyceride analogs are specifically cleared by the liver. Consequently, they offer several advantages over nonspecific urographic agents in their ability to enhance lesion conspicuity in this hepatoma model.

Animals↗
PubMed2003

VLDL-induced triglyceride accumulation in human macrophages is mediated by modulation of LPL lipolytic activity in the absence of change in LPL mass.

Mixed dyslipidemia of phenotype IIB is characterized by elevated levels of very low density lipoprotein (VLDL)-1 and VLDL-2 subfractions and of low density lipoprotein (LDL), which are associated with premature formation of atherosclerotic plaques, characterized by the presence of lipid-rich macrophage foam cells. Lipoprotein lipase (LPL) is a key factor in mediating macrophage lipid accumulation and foam-cell formation from native VLDL particles. The action of macrophage-derived LPL in the induction of intracellular lipid accumulation from triglyceride-rich lipoprotein (TRL) subfractions (VLDL-1, VLDL-2) is, however, indeterminate, as is the potential role of VLDL-1 and VLDL-2 in modulating macrophage LPL expression. We evaluated the role of LPL in the interaction of type IIB VLDL-1 and VLDL-2 with human macrophages. Both VLDL-1 and VLDL-2 subfractions induced significant accumulation of triglyceride (9.8-fold, P<0.0001, and 4.8-fold, P<0.0001, respectively) and of free cholesterol content (1.4-fold, P<0.001, and 1.2-fold, P=0.02, respectively). Specific inhibition (90%) of the lipolytic activity of endogenous LPL by tetrahydrolipstatin (THL) in the presence of VLDL-1 or VLDL-2 resulted in marked reduction in cellular loading of both triglycerides (-89%, P=0.008, and -89%, P=0.015, respectively) and free cholesterol (-76%, P=0.02, and -55%, P=0.06 respectively). Furthermore, VLDL-1 and VLDL-2 induced marked increase in macrophage-derived LPL enzyme activity (+81%, P=0.002, and +45%, P=0.02), but did not modulate macrophage-derived LPL mRNA and protein expression; consequently, LPL specific activity was significantly increased from 1.6 mU/microg at baseline to 4.1 mU/microg (P=0.01) and 3.1 mU/microg (P=0.05), in the presence of VLDL-1 and VLDL-2, respectively. We conclude that type IIB VLDL-1 and VLDL-2 induce triglyceride accumulation in human monocyte-macrophages primarily via the lipolytic action of LPL, which may involve stabilization and activation of the macrophage-secreted enzyme, rather than via modulation of enzyme production.

Cells, Cultured↗
PubMed2000

Effect of microsomal triglyceride transfer protein gene variants (-493G > T, Q95H and H297Q) on plasma lipid levels in healthy middle-aged UK men.

Microsomal triglyceride transfer protein (MTP) plays a central role in the synthesis of lipoproteins by shuttling lipids between phospholipid membranes to apoB. We have examined the effect of three MTP gene variants, -493G > T, Q95H and H297Q, in 2831 healthy UK middle-aged men. The rare allele frequencies were: 0.25 (95% CI 0.24-0.26) for -493T, 0.054 (95% CI 0.05-0.06) for 95H and 0.32 (95% CI 0.31-0.33) for 297Q. The three variants were in strong allelic association in all pairwise combinations (p < 0.001). None of the variant sites were associated with significant differences in cholesterol, triglyceride, apoB or apoAI levels. When stratified by tertiles of triglycerides for the H297Q variant alone there was a significant effect on apoB levels in men in the top tertile (p = 0.01). Considering the -493G > T and H297Q genotype in combination on baseline levels, individuals with three or four rare alleles had 6.6% higher mean apoB levels compared to the rest (p = 0.007). Therefore, homozygosity for 297Q at higher triglyceride (Tg) levels, or in combination with -493G > T, is associated with a raising effect on apoB levels, suggesting the importance of modest differences in MTP activity in determining hepatic secretion of lipoproteins in healthy men.

Alleles↗
PubMed1982

Positional distribution of fatty acids in the triglyceride classes of milk fat.

A sample of milk fat was fractionated into high, medium and low molecular weight triglycerides by silicic acid column chromatography. Each fraction was further separated by silver ion adsorption thin-layer chromatography into triglyceride class which were subjected to stereospecific analysis. Trans-monoene fatty acids were incorporated into triglycerides in the same manner as their cis-isomer. The specific positional distribution for fatty acids in intact mild fat triglycerides was not always maintained in the molecular weight fractions or in the various classes of unsaturation. The significance of these findings is discussed in relation to biosynthetic mechanisms for milk fat synthesis.

Animals↗
PubMed1983

Relationship between fatty acid composition and triglyceride structure of bovine milk fat.

Fourteen samples of milk fat, representing a wide range of individual fatty acid contents, were subjected to stereospecific analysis to determine fatty acid contents at the sn-1-, sn-2- and sn-3-positions of the triglycerides. Highly significant linear relationships were found between the content of a fatty acid at the 3 positions and the content of the same acid in the intact triglycerides. As the content of an acid increased in the triglycerides there were increases in the content of that acid at the 3 positions. When the content of an acid changed in the triglycerides, the content at the 3 stereospecific positions did not change at the same rate. The positions with the highest slope values corresponded to the positions where the individual fatty acids were preferentially esterified.

Animals↗
PubMed2001

Effect of beta-lactoglobulin on plasma retinol and triglyceride concentrations, and fatty acid composition in calves.

Beta-lactoglobulin (beta-lg) is the main protein of ruminant milk whey. Although beta-lg can bind in vitro to a variety of hydrophobic substrates, mainly retinol and long-chain fatty acids, its physiological function is still unknown. In Exp. 1, we investigated the effect of beta-lg on the plasma retinol concentration in preruminant calves. Holstein male calves (n = 20) were fed Holstein whole milk at 40 g/kg body weight (BW) plus vitamin A acetate (500,000 i.u.) with or without beta-lg (0.4 g/kg BW). The plasma retinol concentration of 10-d-old calves was greater (P < 0.05) in the beta-lg-fed group) than in the control group during the period from 8 to 12 h and at 24 h after the feeding. The postprandial change of plasma retinol in 40-d-old calves fed milk with beta-lg was higher (P < 0.05) than that in the control calves only at 12 h after the feeding. In Exp. 2, Holstein male calves (n = 18) were used to investigate the effect of beta-lg on plasma triglyceride concentration and fatty acid composition. Calves were fed Holstein whole milk at 40 g/kg BW plus milk fat prepared from whole milk at 2 g/kg BW with or without beta-lg (0.4 g/kg BW). Plasma triglyceride concentration at age 10 d was higher (P < 0.05) in the beta-lg-fed group than in the controls during the periods from 1 to 2 h and from 7 to 11 h after the feeding. At age 40 d, plasma triglyceride in the beta-lg-fed group was higher (P < 0.05) than in the control group only at 9 h. Ratios of palmitic, stearic, and oleic acids to total plasma lipids were higher (P < 0.05) in the calves fed beta-lg milk than in the control calves at age 10 d. These results suggest that beta-lg enhances the intestinal uptake of retinol, triglyceride, and long-chain fatty acids in preruminant calves.

Animals↗
PubMed2004

A mathematical model for mammary fatty acid synthesis and triglyceride assembly: the role of stearoyl CoA desaturase (SCD).

An increase in the proportion of unsaturated fatty acids in milk is considered desirable for human health. A prerequisite for the manipulation of milk fat composition is a co-ordinated understanding of the complex interactions in its biosynthesis. It has been suggested that an increase in the expression of mammary stearoyl-CoA-desaturase (SCD) would enrich mono-unsaturated fatty acids in milk, and therefore improve its nutritional properties. To investigate the potential effects of changes in expression of mammary enzymes and substrate availability on milk fat composition, we constructed, parameterized and evaluated a mechanistic mathematical model of fatty acid biosynthesis and milk-fat triglyceride assembly. The objective was to describe changes in the amount and composition of milk fat produced by bovine mammary cells due to changes in nutrition. Using the model we found that a 50% up-regulation in SCD activity increased the molar fraction of milk triglyceride 18:1 from 0.30 to 0.33 and 16:1 from 0.04 to 0.06. Up-regulation of SCD therefore did not appear to be the optimal method for increasing the content of unsaturated fatty acids in milk fat. The model was also used to determine the likely rate-limiting processes for the incorporation of unsaturated fatty acids into milk fat. Halving the concentration of glycerol 3-phosphate increased the molar fraction of milk triglyceride 18:1 from 0.30 to 0.35 and decreased the molar fraction of milk triglyceride 16:0 from 0.30 to 0.22. This achieved the desirable outcome of producing more unsaturated low-fat milk. Our model also predicted that a K232A mutation in the bovine mammary DGAT1 gene that is linked with an increase in milk fat yield would be consistent with a 120% increase in the DGAT acylation rate and also would be associated with a decrease in milk mono-unsaturated fatty acids.

Acyltransferases↗
PubMed1989

The role of calcium ions and bile salts on the pancreatic lipase-catalyzed hydrolysis of triglyceride emulsions stabilized with lecithin.

Lecithin-stabilized triglyceride emulsions are subject to hydrolysis by pancreatic lipase. The time profiles of these reactions are characterized by a lag-phase and a zero-order phase. Lag phases are more pronounced with long-chain triglycerides. Ca2+ is effective in reducing the lag-phase and activating lipase. Kinetic analysis of the reactions suggests that, like previous findings by others, taurodeoxycholate (TDC) micellar solutions combine with the lipase-colipase complex to form another catalytically active enzyme form. This enzyme form exhibits reduced activity in the absence of Ca2+. In the presence of Ca2+ the mixed micelle-lipase complex becomes more active and opens a new pathway for lipolysis. It is suggested that this enzyme form can bind more easily to interfaces with different physicochemical properties. Under these conditions, Ca2+ activates the lipolysis of short-, medium-, and long-chain triglycerides by a similar mechanism. Maximum activities were measured in the presence of approximately 6 mM TDC and 30 mM Ca2+. The experimental conditions approximate the physiological conditions in the gastrointestinal tract since all of the factors studied here have been reported to be necessary for in vivo lipolysis and/or absorption of triglycerides. A mechanistic model for lipolysis in the presence of Ca2+ and the bile salt TDC is proposed which accounts for most of the experimental observations in a quantitative manner.

Bile Acids and Salts↗
PubMed2004

Apolipoprotein E structure and substrate and receptor-binding activities of triglyceride-rich human plasma lipoproteins in normo- and hypertriglyceridemia.

Cysteine-arginine interchanges along the primary sequence of human plasma apolipoprotein E (apoE) play an important role in determining its biological functions due to a high mutation frequency of cytosine in CGX triplet that codes 33 of 34 apolipoprotein arginine residues. The contribution of apoE secondary structure to apolipoprotein-lipid interaction is described. The significance of apolipoprotein in triglyceride synthesis, lipoprotein lipolysis, and receptor-mediated clearance of lipolytic remnants of triglyceride-rich lipoproteins is discussed as well. The metabolic flow of lipoproteins in normo- and hypertriglyceridemia can be described by separate compartments that contribute to lipoprotein interaction with at least six different receptors: 1) low density lipoprotein (LDL) receptor; 2) LDL receptor-related protein (LRP); 3) apoB(48) macrophage receptor for hypertriglyceridemic very low density lipoproteins (VLDL); 4) scavenger receptors; 5) VLDL receptor; 6) lipolysis-stimulated receptor. The contribution of the exposure of apoE molecules on the surface of triglyceride-rich particles sensitive both to lipolysis and plasma triglyceride content to the interaction with LDL receptor and LRP is emphasized.

Apolipoproteins E↗
PubMed2000

YM-53601, a novel squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in several animal species.

The aim of this study was to evaluate the potency of YM-53601 ((E)-2-[2-fluoro-2-(quinuclidin-3-ylidene) ethoxy]-9H-carbazole monohydrochloride), a new inhibitor of squalene synthase, in reducing both plasma cholesterol and triglyceride levels, compared with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and fibrates, respectively. YM-53601 equally inhibited squalene synthase activities in hepatic microsomes prepared from several animal species and also suppressed cholesterol biosynthesis in rats (ED(50), 32 mg kg(-1)). In guinea-pigs, YM-53601 and pravastatin reduced plasma nonHDL-C (=total cholesterol - high density lipoprotein cholesterol) by 47% (P<0.001) and 33% (P<0.001), respectively (100 mg kg(-1), daily for 14 days). In rhesus monkeys, YM-53601 decreased plasma nonHDL-C by 37% (50 mg kg(-1), twice daily for 21 days, P<0.01), whereas the HMG-CoA reductase inhibitor, pravastatin, failed to do (25 mg kg(-1), twice daily for 28 days). YM-53601 caused plasma triglyceride reduction in hamsters fed a normal diet (81% decrease at 50 mg kg(-1), daily for 5 days, P<0.001). In hamsters fed a high-fat diet, the ability of YM-53601 to lower triglyceride (by 73%, P<0.001) was superior to that of fenofibrate (by 53%, P<0.001), the most potent fibrate (dosage of each drug: 100 mg kg(-1), daily for 7 days). This is the first report that a squalene synthase inhibitor is superior to an HMG-CoA reductase inhibitor in lowering plasma nonHDL-C level in rhesus monkeys and is superior to a fibrate in significantly lowering plasma triglyceride level. YM-53601 may therefore prove useful in treating hypercholesterolemia and hypertriglyceridemia in humans.

Animals↗
PubMed1998

Breakfasts high in monoglyceride or triglyceride: no differential effect on appetite or energy intake.

OBJECTIVE: To test whether isoenergetic isoenergetically-dense doses of dietary 1-monoglyceride or triglyceride differentially influence appetite and meal-to-meal energy intake in man. DESIGN: Six men and six women were each studied twice in a 2 d protocol. On day 1 (maintenance day) they were fed a medium fat (MF) maintenance diet (MF: 40% fat, 47% carbohydrate and 13% protein by energy) calculated at 1.6 x resting metabolic rate (RMR). On day 2 (manipulation day) at 08.30 h subjects consumed a high-fat breakfast designed to contain 80-85% of RMR, composition 10% protein, 56% fat and 34% carbohydrate by energy, with 65% of energy for fat derived as either 1-monoglyceride or triglyceride. Food and energy intake were monitored at lunch (given at 12.30pm) and throughout the remainder of the day. During this time subjects had ad libitum access to isoenergetic, isoenergetically dense MF (40:47:13) foods (550kJ/100g), until 22.30pm). Subjective hunger and satiety were tracked hourly, during waking hours. RESULTS: There was no significant effect of fat type on food or energy intake at lunch or during the ad libitum period. There was no diet effect on subjective hunger (F(1,10)0.00; P= 0.975) in the inter-meal periods of morning or afternoon, nor during the whole day. Subjects found both diets to be similarly pleasant (F(1,61)0.84;P= 0.364). Men and women responded similarly, except that men ate more on all occasions than women. CONCLUSIONS: This study suggests that when a large dose of l-monoglyceride or triglyceride is incorporated into a breakfast meal, it behaves in a manner that is very similar to triglyceride in terms of the effects on hunger, appetite or feeding behaviour.

Adult↗
PubMed1998

The effect of a low-fat, high-carbohydrate diet on serum high density lipoprotein cholesterol and triglyceride.

OBJECTIVE: To determine whether substituting carbohydrate for saturated fat has any adverse effects on serum high density lipoprotein (HDL) cholesterol and triglycerides in free-living individuals. DESIGN: Randomised crossover trial. SETTING: General community. SUBJECTS: Volunteer sample of 38 healthy free-living men with mean (s.d.) age 37 (7) y, moderately elevated serum total cholesterol 5.51 (0.93) mmol/l and body mass index 26.0 (3.6) kg/m2. INTERVENTIONS: Participants completed two six week experimental periods during which they consumed either a traditional Western diet (36%, 18%, and 43% energy from total, saturated, and carbohydrate, respectively) or a low-saturated fat high-carbohydrate diet (22%, 6% and 59% energy from total, saturated, and carbohydrate, respectively). Dietary principles were reinforced regularly, but food choices were self-selected during each experimental period. MAIN OUTCOME MEASURES: Serum lipids, body weight and plasma fatty acids. RESULTS: Reported energy and nutrient intakes, plasma fatty acids, and a drop in weight from 79.1 (12.5) kg on the Western diet to 77.6 (12.0) kg on the high-carbohydrate diet (P < 0.001) confirmed a high level of compliance with experimental diets. Total and low density lipoprotein (LDL) cholesterol fell from 5.52 (1.04) mmol/l and 3.64 (0.88) mmol/l, respectively on the Western diet to 4.76 (1.10) mmol/l and 2.97 (0.94) mmol/l on the high-carbohydrate diet (P < 0.001). HDL cholesterol fell from 1.21 (0.27) mmol/l on the Western diet to 1.07 (0.23) mmol/l on the high-carbohydrate diet (P = 0.057), but the LDL:HDL cholesterol ratio improved from 3.17 (1.05) on the Western diet to 2.88 (0.97) on the high-carbohydrate diet (P = 0.004). Fasting triglyceride levels were unchanged throughout the study. CONCLUSIONS: Replacement of saturated fat with carbohydrate from grains, vegetables, legumes, and fruit reduces total and LDL cholesterol with only a minor effect on HDL cholesterol and triglyceride. It seems that when free living individuals change to a fibre rich high-carbohydrate diet appropriate food choices lead to a modest weight reduction. This may explain why the marked elevation of triglyceride and reduction of HDL cholesterol observed on strictly controlled high-carbohydrate diets may not occur when such diets are followed in practice.

Adult↗
PubMed2005

Changes in cholesterol and triglyceride concentrations in the Vanguard population of the Carotene and Retinol Efficacy Trial (CARET).

BACKGROUND: The Beta-Carotene and Retinol Efficacy Trial (CARET) was terminated 21 months ahead of schedule due to an excess of lung cancers. Deaths from cardiovascular disease also increased (relative risk=1.26 (95% confidence interval (CI) 0.99-1.61)) in the group assigned to a combination of 30 mg beta-carotene and 25 000 IU retinyl palmitate (vitamin A) daily. The basis for increased cardiovascular mortality is unexplained. DESIGN: We analyzed data on serum lipids, available for 1474 CARET Vanguard participants who were enrolled in the two CARET pilot studies and transitioned to the Vanguard study. Total cholesterol and triglycerides were measured 2 months prior to, 4 and 12 months following randomization, and annually thereafter for up to 7 y. INTERVENTION: In the asbestos-exposed pilot (N = 816), participants were assigned to beta-carotene and retinol or to placebo; in the smokers pilot (N = 1029), participants were assigned to beta-carotene, retinol, a combination, or placebo. RESULTS: Serum cholesterol showed a decline over time in both arms; serum triglycerides had a continuous decline over time in the placebo arm, but an initial increase that persisted in the active arm. Both serum cholesterol concentrations (P < 0.0003) and serum triglycerides (P < 0.0001) were significantly higher in the participants receiving vitamin A and/or a combination of vitamin A and beta-carotene (n = 863) as compared to the placebo group (n = 611). Those in this active intervention group had an average cholesterol concentration 5.3 mg/dl (0.137 mmol/l) higher than those in the placebo arm. CONCLUSION: The differences in cholesterol and triglyceride concentrations between the groups following randomization may account in part for the unexpected excess in cardiovascular deaths seen in the active intervention arm of CARET.

Antioxidants↗
PubMed2006

Association of beta2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels.

Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The beta(2) adrenergic receptor (beta(2)-AR) gene may constitute a potential candidate gene to explain part of the genetic predisposition to human obesity and correlated traits. With regard to the association between beta(2)-AR gene polymorphisms and obesity-related metabolic disorders, published reports give conflicting results. We investigated the role of three polymorphisms, and related haplotypes of the beta(2)-AR in the obesity and related traits in a cohort of overweight/obese subjects. We characterized one single nucleotide polymorphism (SNP) in the promoter region (5'LC-Cys19Arg) and two in the coding region (Gly16Arg and Gln27Glu) of the beta(2)-AR in 642 consecutively recruited overweight/obese subjects in whom extensive clinical and biochemical analysis was performed. The effect of the polymorphisms on quantitative variables was investigated using multiple linear regression analysis. 5'LC-Cys19 homozygous showed higher triglyceride and LDL-cholesterol levels compared to 5'LC-Arg19 homozygous (P=0.03 and P=0.01, respectively). Similar increase in triglyceride and LDL-cholesterol levels was observed for Arg/Arg genotype compared to Gly/Gly genotype of Gly16Arg polymorphism (P=0.02 and P=0.01, respectively) and for Gln/Gln genotype compared to Glu/Glu genotype of the Gln27Glu polymorphism (P=0.01 and P=0.03, respectively). The 5'LC-Cys(19)Arg(16)Gln(27) haplotype determined a significant increase in triglyceride and LDL-cholesterol levels compared to 5'LC-Arg(19)Gly(16)Glu(27) haplotype (P=0.05 and P=0.02, respectively). Our findings provide additional weight to previous observations on the influence of these three genetic variants on lipid phenotypes; particularly on the increase of triglycerides and LDL-cholesterol levels in overweight/obese subjects carrying the 5'LC-Cys(19)Arg(16)Gln(27) haplotype.

Cholesterol, LDL↗