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PubMed1996

Transient hypertriglyceridemia of infancy.

A premature boy who had suffered from IRDS, bronchopulmonary dysplasia and retinopathy of prematurity developed massive hypertriglyceridemia (48.1 mmol/L) together with moderate hypercholesterolemia (12.6 mmol/L) at 5 months of age. Lipoprotein electrophoresis revealed a marked elevation of the level of the very low density lipoprotein fraction. There was a moderate decrease in the activity of a lipolytic enzyme, lipoprotein lipase (LPL). The child had neither liver or renal disorder nor any inflammatory disease. The hyperlipidemia disappeared spontaneously at the age of 3 years. The cause of the decreased LPL activity could not be established. A partial genetic deficiency in lipoprotein lipase appears the most likely explanation, since no signs of secondary lowering of LPL activity could be found.

Child, Preschool↗

PubMed2006

High doses of bifendate elevate serum and hepatic triglyceride levels in rabbits and mice: animal models of acute hypertriglyceridemia.

AIM: To investigate the effects of bifendate on serum and hepatic lipids level in rabbits and mice. METHODS: Animals were administered bifendate [powdered pill suspended in 0.5% sodium carboxymethylcellulose (CMC)] at increasing doses (0.25-1 g/kg, ig). Blood lipid and apolipoprotein levels were measured using commercially available assay kits. RESULTS: The treatment of rabbits with a single dose of bifendate (0.3 g/kg) caused a time-dependent and biphasic change in serum triglyceride (TG) levels, with the value reaching a maximum (3-fold increase compared to the baseline value) between 24 and 36 h post-dosing. When mice were orally treated with bifendate (0.25-1 g/kg), serum TG levels increased by 39%-76% and 14%-39% at 24 and 48 h post-dosing, respectively. When given at daily doses of 0.25 and 1 g/kg for 4 d, bifendate increased serum TG levels (56%-79%), with concomitant elevations in apolipoprotein A-I and apolipoprotein B levels at 24 h after the last dosing. TG levels were also increased (11%-43%) in liver samples of mice receiving single or multiple doses of bifendate. However, bifendate treatment caused slight reductions in serum and hepatic total cholesterol levels (9%-13%). The hypertriglyceridemia induced by bifendate was ameliorated by fenofibrate but not inositol nicotinate treatment in mice. CONCLUSION: The findings suggest that bifendate treatment at high oral doses can cause an acute elevation in serum and hepatic TG levels.

Animals↗

PubMed1996

Differential effects of acute hypertriglyceridemia on insulin action and insulin receptor autophosphorylation.

Experimentally induced hypertriglyceridemia (HTG) and high plasma free fatty acid (FFA) levels impair in vivo insulin action. To determine if this is a consequence of impaired in vivo insulin receptor autophosphorylation and related to defective receptor signaling, hyperinsulinemic euglycemic clamps, indirect calorimetry, and skeletal muscle biopsies were performed in nine healthy subjects. In vivo insulin action was determined from the glucose infusion rate (GINF) and glucose oxidation (Glcox) during 40 and 120 mU/m2 /min clamps with (HTG clamp) and without (control clamp) a triglyceride emulsion infusion. The percentage of receptors autophosphorylated in vivo was determined by 125I-labeled insulin tracer binding in skeletal muscle immunoprecipitates of insulin receptors and phosphorylated receptors. Compared with the control clamps, plasma triglycerides and FFA increased four- and twofold, whereas GINF and Glcox decreased 15 and 35%, respectively, during the HTG clamps (all P<0.05). However, the percentages of receptors phosphorylated after the 40 and 120 mU/m2/min HTG clamps (9.2 +/- 1.5 and 21.1 +/- 2.6%, respectively) were similar to the control clamps (9.0 +/- 0.6 and 18.6 +/- 2.2%, respectively). These results indicate that, if impaired insulin signal transduction is a mechanism by which HTG and FFA impair insulin action, it occurs at a site downstream from insulin receptor autophosphorylation.

Adult↗

PubMed2004

Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients.

We evaluated the influence of chronic hypertriglyceridemia and endothelial dysfunction on myocardial glucose uptake (MGU) in Type 2 diabetic patients without coronary heart disease. Patients were divided into two groups according to fasting triglyceride (TG) levels: 5.4 +/- 1.1 and 1.5 +/- 0.3 mmol/l for high- and normal-TG groups, respectively. Five subjects were assigned to the high-TG group and 11 to the normal-TG group. Age, gender, body mass index, systolic and diastolic blood pressure, glucose, insulin, HbA1c, cholesterol, and HDL cholesterol were similar in the two groups, whereas free fatty acid (FFA) levels were higher in the high-TG group basally and at the end of the clamp. Furthermore, five healthy subjects were subjected to the same protocol and used as the control group. MGU was assessed by using 18F-labeled 2-fluoro-2-deoxy-D-glucose under hyperglycemic-hyperinsulinemic conditions. Basal endothelin-1 and nitric oxide levels were significantly higher in the high-TG group than in the normal-TG and control groups, and cGMP and maximal postischemic vasodilation were significantly decreased in the high-TG group compared with the normal-TG and control groups. However, significant alterations were found in the same parameters in the normal-TG group compared with the control group. By the end of the hyperglycemic clamp, in the high-TG group, MGU was approximately 40 and 65% of that in the normal-TG and control groups. MGU negatively correlated with TG, FFA, and endothelin-1, whereas a positive correlation was found with cGMP and maximal postischemic vasodilation. In conclusion, increased TG and FFA levels are risks, in addition to Type 2 diabetes mellitus, for myocardial insulin resistance, endothelial dysfunction, and alteration of nitric oxide/cGMP levels.

Case-Control Studies↗

PubMed2001

Resistance exercise training reduces hypertriglyceridemia in HIV-infected men treated with antiviral therapy.

Hypertriglyceridemia, peripheral insulin resistance, and trunk adiposity are metabolic complications recently recognized in people infected with human immunodeficiency virus (HIV) and treated with highly active antiretroviral therapy (HAART). These complications may respond favorably to exercise training. Using a paired design, we determined whether 16 wk of weight-lifting exercise increased muscle mass and strength and decreased fasting serum triglycerides and adipose tissue mass in 18 HIV-infected men. The resistance exercise regimen consisted of three upper and four lower body exercises done for 1-1.5 h/day, 4 days/wk for 64 sessions. Dual-energy X-ray absorptiometry indicated that exercise training increased whole body lean mass 1.4 kg (P = 0.005) but did not reduce adipose tissue mass (P = NS). Axial proton-magnetic resonance imaging indicated that thigh muscle cross-sectional area increased 5-7 cm(2) (P < 0.005). Muscle strength increased 23-38% (P < 0.0001) on all exercises. Fasting serum triglycerides were decreased at the end of training (281-204 mg/dl; P = 0.02). These findings imply that resistance exercise training-induced muscle hypertrophy may promote triglyceride clearance from the circulation of hypertriglyceridemic HIV-infected men treated with antiviral therapy.

Adipose Tissue↗

PubMed1988

Investigation of hypertriglyceridemia in small for gestational age fetuses.

Plasma triglyceride, nonesterified fatty acid (NEFA), glycerol, insulin and blood glucose concentrations were measured in 32 small for gestational age (SGA) and 54 appropriate for gestational age fetuses. Although the values of plasma NEFA and glycerol concentrations were not different in the two groups, some SGA fetuses were hypertriglyceridemic, hypoglycemic and hypoinsulinemic. These findings suggest that hypertriglyceridemia in hypoxemic SGA fetuses is not due to lipolysis, nor to increased triglyceride synthesis, but rather to impaired utilization of circulating triglycerides.

Blood Glucose↗

PubMed1992

Delayed clearance of postprandial chylomicrons and their remnants in the hypoalphalipoproteinemia and mild hypertriglyceridemia syndrome.

Hypoalphalipoproteinemia (HPAL) with mild hypertriglyceridemia (HTG) is associated with increased coronary artery disease (CAD) risk. The aim of this study was to examine the metabolism of postprandial lipoproteins in HPAL/HTG subjects (n = 21). They had a fasting plasma high density lipoprotein (HDL) cholesterol level < 0.9 mmol/l, a triglycerides (TG) level of 2.0-7.1 mmol/l, and a normal low density lipoprotein (LDL) cholesterol level (< 3.7 mmol/l). They were either homozygous for apoprotein E3 (n = 13) or heterozygous for apoprotein E4 (n = 5) or E2 (n = 3). After ingestion of a vitamin A fat load, plasma and chylomicron (CM) retinyl palmitate (RP) response (areas under curves) was three times and non-CM RP response 2.5 times greater than in normolipidemic control subjects (n = 13). There was close correlation between fasting plasma TG level and postprandial RP response in HPAL/HTG subjects (plasma, r = 0.87; CM, r = 0.89; and non-CM, r = 0.84). In control subjects this correlation was present for plasma RP (r = 0.80) and CM RP (r = 0.61) but not for non-CM RP (r = 0.53). In contrast, postprandial RP response was not correlated with fasting plasma HDL cholesterol levels for both groups. There was also no correlation between fasting TG and fasting HDL cholesterol. Postheparin lipoprotein lipase and hepatic lipase activities were slightly higher in HPAL/HTG subjects. The pattern of postprandial change in HDL composition was similar to that in control subjects. These data indicate enhanced postprandial lipemia in the HPAL/HTG syndrome, and this may account for their increased CAD risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Persistence of abnormalities in metabolism of apolipoproteins B-100 and A-I after weight reduction in patients with primary hypertriglyceridemia.

Obesity commonly accompanies hypertriglyceridemia, and weight reduction is widely recommended for treatment of elevated triglyceride levels. To determine whether weight reduction will normalize lipoprotein metabolism in overweight, hypertriglyceridemic patients, 10 such male patients underwent weight loss until their body weights were within the desirable range. After reestablishment of a steady state in body weight at the lower level, measurements were made of plasma lipid, lipoprotein, and apolipoprotein levels and the kinetics of low density lipoprotein (LDL) apolipoprotein B-100 (apo B) and apolipoprotein A-I (apo A-I). The patients lost an average of 10.6 +/- 2.1 kg (mean +/- SEM). Plasma triglyceride concentrations fell from 431 +/- 42 mg/dl to 248 +/- 27 mg/dl (p less than 0.001), whereas concentrations of total cholesterol, LDL cholesterol, total apo B, and high density lipoprotein (HDL) cholesterol were unchanged after weight loss. On average, the fractional catabolic rates (FCRs) for LDL were much higher in the patients after weight loss than in 16 normal control subjects (0.55 +/- 0.06 versus 0.31 +/- 0.06 pool/day), and input rates for LDL also were higher for hypertriglyceridemic patients after weight loss (22.2 +/- 2.4 versus 12.8 +/- 2.3 mg/kg.day). Compared with 20 normal control subjects, hypertriglyceridemic patients after weight reduction had persistent low HDL cholesterol levels (32 +/- 2 versus 54 +/- 3 mg/dl) as well as low apo A-I levels (99 +/- 5 versus 122 +/- 4 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Insulin resistance, glucose intolerance, and hyperinsulinemia. Hypertriglyceridemia versus hypercholesterolemia.

Plasma glucose and insulin responses to oral glucose and mixed meals and the ability of insulin to stimulate glucose disposal were quantified in normal volunteer subjects and patients with types IIA, IIB, and IV hyperlipoproteinemia (HLP). The results indicated that patients with either type IIB or IV HLP had higher plasma glucose (p < 0.05-< 0.001) and insulin (p < 0.001) responses to both oral glucose and mixed meals compared with the normal subjects and patients with type IIA HLP. Steady-state plasma glucose concentrations (mmol/L) were also higher (p < 0.001) in patients with types IIB (13.3 +/- 0.6) and IV (12.8 +/- 1.2) HLP during a continuous infusion of somatostatin, glucose, and insulin than either the control group (volunteer subjects) (6.2 +/- 0.9) or patients with type IIA HLP (5.6 +/- 1.0). Because the steady-state plasma insulin concentrations were similar in all four groups, patients with either type IIB or IV HLP were resistant to insulin-mediated glucose uptake. These data indicate that patients with hypertriglyceridemia are insulin resistant, glucose intolerant, and hyperinsulinemic, irrespective of the plasma cholesterol concentration. The results further demonstrate that hypercholesterolemic patients with normal triglyceride concentrations do not have any abnormalities of glucose and insulin metabolism.

Adult↗

PubMed1993

Effects of lovastatin on the levels, structure, and atherogenicity of VLDL in patients with moderate hypertriglyceridemia.

The purpose of this study was to determine whether lovastatin treatment reduced very low density lipoprotein (VLDL) abnormalities in hypertriglyceridemic subjects. Lovastatin reduced plasma triglyceride levels and the levels of total VLDL, intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) cholesterol. The numbers of VLDL particles of Sf 100-400 and Sf 60-100 but not Sf 20-60 particles were reduced by lovastatin, as was the amount of cholesteryl ester per particle. All VLDL subspecies bound to the LDL receptor of cultured human fibroblasts with similar, high affinities on both placebo and lovastatin, but VLDL Sf 100-400 and VLDL Sf 60-100 caused less suppression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase activity after lovastatin therapy, indicating reduced LDL receptor-mediated cholesterol delivery. The average decrease in reductase suppression by VLDL Sf 100-400 after lovastatin was 32%, similar to the 34% average decrease in cholesteryl ester content of VLDL Sf 100-400 after lovastatin. Although statistical significance was not achieved, there was a trend toward decreased VLDL Sf 100-400-induced rapid, receptor-mediated triglyceride accumulation in P388D1 macrophages after lovastatin. Taken together, these observations suggest that lovastatin may be of potential benefit in decreasing the atherosclerotic complications of hypertriglyceridemia.

Adult↗

PubMed1995

Overexpression of human lipoprotein lipase protects diabetic transgenic mice from diabetic hypertriglyceridemia and hypercholesterolemia.

We investigated the role of the overexpression of lipoprotein lipase (LPL) in lipoprotein abnormalities in transgenic mice with streptozotocin-induced diabetes mellitus. Before the induction of diabetes, LPL activity was 4.6-fold in skeletal muscle and 2.0-fold higher in the heart in transgenic mice than in their nontransgenic littermates. LPL activity in skeletal muscles in diabetic nontransgenic mice and cardiac LPL activity in diabetic nontransgenic and transgenic mice were decreased. Body weights were similarly reduced, and no appreciable amount of adipose tissue was observed in diabetes in both groups. The plasma triglyceride level was lower in diabetic transgenic mice than in diabetic nontransgenic mice (33.2 +/- 22.5 versus 185.3 +/- 57.4 mg/dL). Induction of diabetes was associated with a significant increase in the plasma cholesterol level in nontransgenic mice (90.0 +/- 11.1 versus 163.9 +/- 39.3 mg/dL) but much less in transgenic mice. Our results indicate that overexpression of LPL in transgenic mice inhibited diabetes-associated hypertriglyceridemia and hypercholesterolemia but did not affect the loss of body weight induced by diabetes.

Animals↗

PubMed1998

Very-low-density lipoprotein response element in the promoter region of the human plasminogen activator inhibitor-1 gene implicated in the impaired fibrinolysis of hypertriglyceridemia.

Hypertriglyceridemia and impaired fibrinolytic function are linked to coronary heart disease and other atherothrombotic disorders. Triglyceride-rich lipoproteins may attenuate fibrinolysis by increasing the plasma levels of plasminogen activator inhibitor-1 (PAI-1). Furthermore, a common 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene has been indicated to influence plasma PAI-1 activity and to be involved in an allele-specific response to triglycerides. Herein we show by transfection assays that VLDLs induce transcription of the human PAI-1 promoter in endothelial cells. A VLDL response element (VLDLRE) is located to residues -672 to -657 in the promoter region by electromobility shift assay, methylation interference, and DNase I footprinting, and its activity is shown to be influenced by the common 4G/5G polymorphism located adjacent to and upstream of the binding site of a VLDL-inducible transcription factor. These findings may provide a molecular explanation to the link between VLDL and PAI-1 activity elevation in plasma and to the interaction between the 4G/5G polymorphism and plasma triglycerides.

Base Sequence↗

PubMed2000

Normal oxidative stress and enhanced lipoprotein resistance to in vitro oxidation in hypertriglyceridemia: effects of bezafibrate therapy.

Although there is evidence that hyperlipidemia and predominance of small dense low density lipoproteins (LDLs) are associated with increased oxidative stress, the oxidation status in patients with hypertriglyceridemia (HTG) has not been studied in detail. Therefore, we studied urinary levels of F(2)-isoprostanes (8-isoprostaglandin F(2alpha) and 2,3-dinor-5,6-dihydro-8-isoprostaglandin F(2alpha)) and susceptibility of very low density lipoproteins (VLDLs) and LDLs to oxidation ex vivo in 18 patients with endogenous HTG and 20 matched control subjects. In addition, the effects of 6 weeks of bezafibrate therapy were assessed in a double-blind, placebo-controlled, crossover trial. Urinary levels of F(2)-isoprostanes were similar in the HTG and normolipidemic group. Bezafibrate caused an increase in 8-isoprostaglandin F(2alpha) (762+/-313 versus 552+/-245 ng/24 h for bezafibrate and placebo therapy, respectively; P=0.03), whereas 2,3-dinor-5, 6-dihydro-8-isoprostaglandin F(2alpha) levels tended to be increased (1714+/-761 versus 1475+/-606 ng/24 h for bezafibrate and placebo therapy, respectively; P=0.11). VLDLs and LDLs were more resistant to copper-induced oxidation in patients with HTG than in control subjects. Bezafibrate reversed the oxidation resistance to the normal range. In conclusion, these results indicate the following: (1) HTG is associated with normal in vivo oxidative stress and enhanced ex vivo resistance of lipoproteins to oxidation. (2) Bezafibrate reduces the resistance of lipoproteins to copper-induced oxidation and enhances oxidative stress in HTG patients.

Bezafibrate↗

PubMed2000

Not acute but chronic hypertriglyceridemia is associated with impaired endothelium-dependent vasodilation: reversal after lipid-lowering therapy by atorvastatin.

There is controversy regarding the relation between hypertriglyceridemia (HTG) and endothelial function. This study was designed to investigate endothelial function in a patient group with chronic HTG, before and during lipid-lowering therapy by atorvastatin. In addition, the effects of acute HTG on endothelial function were studied in normolipidemic individuals. Eight male patients with chronic HTG were studied before and after 6 weeks of lipid-lowering treatment with 80 mg atorvastatin once daily. Ten age-matched control subjects were studied at baseline and immediately after a high-dose infusion of artificial triglycerides. The endothelium-dependent response to serotonin was attenuated in the HTG group, whereas the response to acetylcholine was comparable to the response in the control group. The response to the endothelium-independent vasodilator nitroprusside was comparable in both groups. In response to atorvastatin therapy, serum triglyceride and cholesterol levels decreased significantly by 43% (paired t test, P=0.017) and 38% (paired t test, P=0.012), respectively. After 6 weeks of treatment, the forearm blood flow response to serotonin improved from 63% to 106% (ANOVA, P<0.001). Induction of acute HTG in the control subjects did not affect the forearm blood flow responses to serotonin and nitroprusside; however, the response to acetylcholine was paradoxically increased. In conclusion, patients with chronic HTG have an impaired endothelium-dependent vasodilation to serotonin that is normalized after 6 weeks of lipid-lowering therapy by atorvastatin.

Acetylcholine↗

PubMed2000

Apolipoprotein E2 (Lys146-->Gln) causes hypertriglyceridemia due to an apolipoprotein E variant-specific inhibition of lipolysis of very low density lipoproteins-triglycerides.

The apolipoprotein E2 (Lys146-->Gln) variant is associated with a dominant form of familial dysbetalipoproteinemia. Heterozygous carriers of this variant have elevated levels of plasma triglycerides, cholesterol, and apolipoprotein E (apoE). It was hypothesized that the high amounts of triglycerides in the very low density lipoprotein (VLDL) fraction are due to a disturbed lipolysis of VLDL. To test this hypothesis, apoE knockout mice were injected with an adenovirus containing the human APOE*2 (Lys146-->Gln) gene, Ad-E2(146), under the control of the cytomegalovirus promoter. ApoE knockout mice injected with an adenovirus vector encoding human apoE3 (Ad-E3) were used as controls. Five days after adenovirus injection, plasma cholesterol levels of mice injected with a high dose of Ad-E2(146) (2x10(9) plaque-forming units) were not changed compared with preinjection levels, whereas in the group who received a low dose of Ad-E2(146) (5x10(8) plaque-forming units) and in the groups injected with a low or a high dose of Ad-E3, plasma cholesterol levels were decreased 5-, 6-, and 12-fold, respectively. Plasma triglycerides were not affected in mice injected with Ad-E3. In contrast, a 7-fold increase in plasma triglycerides was observed in mice injected with the low dose of Ad-E2(146) compared with mice injected with Ad-E3. Injection with the high dose of Ad-E2(146) resulted in a dramatic increase of plasma triglycerides (50-fold compared with Ad-E3 injection). In vitro lipolysis experiments showed that the lipolysis rate of VLDLs containing normal amounts of apoE2 (Lys146-->Gln) was decreased by 54% compared with that of VLDLs containing comparable amounts of apoE3. The in vivo VLDL-triglyceride production rate of Ad-E2(146)-injected mice was not significantly different from that of Ad-E3-injected mice. These results demonstrate that expression of apoE2 (Lys146-->Gln) causes hypertriglyceridemia due to an apoE variant-specific inhibition of the hydrolysis of VLDL-triglycerides.

Adenoviridae↗

PubMed1993

Mechanism of hypertriglyceridemia in Dahl rats.

Plasma triglyceride concentrations were shown to be higher in hypertensive (153 +/- 2 mm Hg) male Dahl salt-sensitive rats than in control Sprague-Dawley rats (122 +/- 2 mm Hg). These differences in triglyceride concentrations were seen when blood was drawn at 9 AM from unfasted animals (229 +/- 27 versus 111 +/- 8 mg/dL), at 1 PM after a 4-hour fast (186 +/- 13 versus 88 +/- 4 mg/dL), or at 9 AM after a 13-hour fast (151 +/- 6 versus 90 +/- 6 mg/dL), all p < 0.001. Total triglyceride secretion was also compared in groups of rats by determining the increment in plasma triglyceride concentration for 2 hours after blocking triglyceride removal from plasma by injecting Triton. Studies performed at 1 PM and 9 AM, after the 4- and 13-hour fast, demonstrated that total triglyceride secretion was greater (p < 0.05) in Dahl rats only when studied at 1 PM. Direct estimates of hepatic triglyceride secretion at 1 PM also demonstrated a significant (p < 0.02) increase in secretion rate by perfused livers from Dahl rats, due in part to their increased liver size. In addition, removal of prelabeled very low density lipoprotein-triglyceride in the intact rat was significantly (p < 0.05) decreased in Dahl rats. Lipoprotein lipase activity measured in skeletal muscle, heart, and adipose tissue was also significantly decreased at 9 AM and 1 PM (after 0 and 4 hours of fasting) in tissue from Dahl rats. These data confirm that Dahl rats have higher plasma triglyceride concentrations than Sprague-Dawley rats. Since both total and hepatic triglyceride secretion were somewhat greater in Dahl rats, in association with a decrease in both removal of very low density lipoprotein from plasma and decreased muscle and adipose tissue lipoprotein lipase activity, it seems likely that hypertriglyceridemia in Dahl rats results from a combination of increased triglyceride secretion and decreased triglyceride removal.

Adipose Tissue↗

PubMed2002

Association between SAH, an acyl-CoA synthetase gene, and hypertriglyceridemia, obesity, and hypertension.

BACKGROUND: The SA gene (SAH) has been isolated by differential screening from a genetically hypertensive rat strain as a candidate gene that may contribute to hypertension. Recently, the SA protein has been reported to be highly homologous to bovine xenobiotic-metabolizing medium-chain fatty acid:CoA ligase. METHODS AND RESULTS: To clarify the pathophysiological significance of SAH, we searched for polymorphisms of human SAH and performed association studies using a large cohort (4000 subjects) representing the general population in Japan. We found 2 polymorphisms in the promoter region and single-nucleotide polymorphisms in introns 5, 7, and 12 and exon 8. One of the variants, an A/G polymorphism in intron 12, just 7 bp upstream from exon 13, strongly affected plasma triglyceride, plasma cholesterol, body mass index (BMI), waist-to-hip ratio (W/H), and blood pressure status. The effect of this genotype on blood pressure seems to be conveyed through its effects on BMI and W/H. Transient expression of the SA protein in mammalian cells confirmed that it is expressed in mitochondria and has medium-chain fatty acid:CoA ligase activity. The A/G polymorphism was found to be associated with the expression level of SA mRNA in peripheral mononuclear cells in vivo. CONCLUSIONS: The G allele of SAH was found to be associated with multiple risk factors, including hypertriglyceridemia, hypercholesterolemia, obesity, and hypertension. This observation should open a new area for future research in multiple-risk-factor syndromes.

Alleles↗

PubMed1991

Increased apo A-I and apo A-II fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia.

Low HDL-cholesterol (HDL-C) levels may elevate atherosclerosis risk, and often associate with hypertriglyceridemia (HTG); however, the metabolic causes of low HDL-C levels with or without HTG are poorly understood. We studied the turnover of radioiodinated HDL apolipoproteins, apo A-I and apo A-II, in 15 human subjects with low HDL-C, six with normal plasma TG levels (group 1) and nine with high TG (group 2), and compared them to 13 control subjects with normal HDL-C and TG levels (group 3). The fractional catabolic rate (FCR) was equally elevated in groups 1 and 2 vs. group 3 for both apo A-I (0.313 +/- 0.052 and 0.323 +/- 0.063 vs. 0.245 +/- 0.043 pools/d, P = 0.003) and apo A-II (0.213 +/- 0.036 and 0.239 +/- 0.037 vs. 0.185 +/- 0.031 pools/d, P = 0.006). Thus, high FCR characterized low HDL-C regardless of the presence or absence of HTG. In contrast, transport rate (TR) of apo A-I did not differ significantly among the groups and the apo A-II TR differed only between groups 2 and 3 (2.15 +/- 0.57, 2.50 +/- 0.39, and 1.83 +/- 0.48 mg/kg per d for groups 1 to 3, respectively, P = 0.016). Several HDL-related factors were similar in groups 1 and 2 but differed in group 3, as with FCR, including the ratio of lipoprotein lipase to hepatic lipase activity (LPL/HL) in post-heparin plasma, the ratio of the HDL-C to apo A-I plus apo A-II levels, and the percent of tracer in the d greater than 1.21 fraction. In linear regression analysis HDL-C levels correlated inversely with the FCR of apo A-I and apo A-II (r = -0.74, P less than 0.0001 for both). Major correlates of FCR were HDL-C/apo A-I + apo A-II, LPL/HL, and plasma TG levels. We hypothesize that lipase activity and plasma TG affect HDL composition which modulates FCR, which in turn regulates HDL-C. Thus, HTG is only one of several factors which may contribute to elevated FCR and low HDL-C. Given the relationship of altered HDL composition with high FCR and low HDL-C levels, factors affecting HDL composition may increase atherosclerosis susceptibility.

Apolipoprotein A-I↗