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PubMed1998

Streptozotocin-induced diabetic cynomolgus monkey is a model of hypertriglyceridemia with low high-density lipoprotein cholesterol.

Hypertriglyceridemia with low high-density lipoprotein (HDL) cholesterol is a risk factor of cardiovascular disease. We attempted to create an animal model of hypertriglyceridemia with low HDL cholesterol by intravenously injecting 30 mg/kg body weight streptozotocin (STZ) to cynomolgus monkeys. This induced hypoinsulinemia and resulted in a decrease in postheparin plasma lipoprotein lipase (LPL) activity and LPL enzyme mass, reduction of plasma HDL cholesterol and elevation of triglycerides. Low HDL cholesterol subsequently caused a reduction of HDL2b cholesterol, while hypertriglyceridemia caused an elevation of very low-density lipoprotein (VLDL) triglyceridemia. Apolipoprotein CII, a co-factor of LPL, was not affected by STZ administration. These results show that hypertriglyceridemia with low HDL cholesterol results from a reduction of LPL activity without affecting apolipoprotein CII after STZ administration. The STZ-induced diabetic cynomolgus monkey is a model of hypertriglyceridemia with low HDL cholesterol, and may be potentially beneficial for studying atherosclerosis caused by hypertriglyceridemia with low HDL cholesterol.

Animals↗
PubMed2006

Pro12Ala sequence variant of the PPARG gene is associated with postprandial hypertriglyceridemia in non-E3/E3 patients with the metabolic syndrome.

BACKGROUND: Postprandial hypertriglyceridemia, a component of the metabolic syndrome, has varied etiology and involves many genes related to triglyceride metabolism. Variations in these genes may affect postprandial hypertriglyceridemia in the context of the metabolic syndrome. METHODS: We orally administered 60 g of fat overload to 74 patients with the metabolic syndrome. We then measured baseline concentrations of cholesterol, triglycerides, HDL cholesterol, apolipoprotein AI, apolipoprotein B, uric acid, and uric acid excretion; we also performed homeostasis model assessments of insulin resistance and insulin sensitivity. At 3 h, we measured triglycerides, cholesterol, apolipoprotein AI, and apolipoprotein B. Patients were considered to have postprandial hypertriglyceridemia if the difference in plasma triglycerides between baseline and 3 h after the test was 1.71 mmol/L or more. We also measured anthropometrical variables and classified the patients according to their peroxisome proliferative activated receptor, gamma (PPARG) gene and apolipoprotein E (APOE) genotype. RESULTS: Postprandial hypertriglyceridemia occurred in 64.7% of patients with the Ala12 allele vs 19.9% of the Pro12Pro patients, (P = 0.00032; odds ratio, 7.6), and in 87.5% of the patients with both the Ala12 allele and the non-E3/E3 APOE genotype (odds ratio, 23.8). Logistic regression analysis showed that PPARG and APOE sequence variants were associated with the presence of postprandial hypertriglyceridemia. CONCLUSION: The Pro12Ala PPARG sequence variant together with a non-E3/E3 APOE genotype is associated with a high risk for postprandial hypertriglyceridemia in patients with the metabolic syndrome, indicating a close association between these genes and the regulation of lipoproteinase clearance.

Apolipoprotein E3↗
PubMed1992

Hypertriglyceridemia in different degrees of glucose intolerance in a Finnish population-based study.

OBJECTIVE: To determine the prevalence of hypertriglyceridemia and the mean serum triglyceride concentrations in different degrees of glucose tolerance--non-insulin-dependent diabetes mellitus (NIDDM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). In addition, we analyzed the correlates of serum triglyceride concentration to explain why it is more prevalent in diabetic subjects. RESEARCH DESIGN AND METHODS: This study was a cross-sectional survey of 4000 people aged 45-64 yr randomly drawn from the population register of the Finnish population of the provinces of North Karelia and Kuopio in eastern Finland and Turku/Loimaa area in southwestern Finland and stratified by four 10-yr age- and sex groups. The final material comprised 96 subjects with NIDDM, 102 subjects with IGT, and 323 subjects with normal glucose tolerance classified on the basis of two 2-h oral glucose tolerance tests. The prevalence of hypertriglyceridemia by the glucose tolerance status and the variation in serum triglycerides associated with selected life-style and biochemical factors were executed as the main outcome measures. RESULTS: The prevalence of hypertriglyceridemia (greater than or equal to 2.3 mM) was 47.6% (95% confidence interval [CI] 32.5-62.7%) in NIDDM men, 21.9% (95% CI 7.6-36.2%) in IGT men, and 15.4% (95% CI 9.3-21.5%) in NGT. In women, hypertriglyceridemia was found in 51.9% (95% CI 38.6-65.2%) among those with NIDDM, 25.7% (95% CI 15.5-35.9%) among those with IGT, and 10.7% (95% CI 6.3-15.1%) in women with NGT. After adjusting for body mass index (BMI) and age, the difference in the prevalence of hypertriglyceridemia between the glucose tolerance groups remained significant in both men (P = 0.008) and women (P = 0.0001). High serum total cholesterol, high BMI, high waist-hip ratio, and low high-density lipoprotein (HDL) cholesterol were significantly associated with high serum triglycerides in all glucose tolerance groups. No synergistic effect between these parameters and glucose tolerance status was found. In multiple linear regression analyses, fasting plasma insulin, diabetes status, and serum uric acid were significant predictors of serum triglyceride concentration after taking into account age, BMI, and HDL and total cholesterol. The association between BMI and serum triglycerides in the regression analysis was significant only when plasma insulin was not included in the model. CONCLUSIONS: Hypertriglyceridemia is common in subjects with NIDDM and IGT and is often associated with low HDL cholesterol, high total cholesterol, hyperinsulinemia, and elevated serum uric acid concentration.

Adult↗
PubMed1999

[Hypertriglyceridemia: danger for the arteries].

AN INDEPENDENT RISK FACTOR: Although debate continues on the epidemiological impact, all surveys report that elevated serum triglyceride is an important risk factor in one-way analysis. More recent case-control studies in patients with premature coronary artery disease have shown that total triglyceride and VLDL levels discriminate better between subjects with and without coronary artery disease. Angiographic studies demonstrate that elevated serum triglyceride is found in coronary artery disease patients and that elevated VLDL or IDL is associated with severity. This relationship is persistently found when the serum cholesterol is taken into consideration but is no longer significant in most of the multivariate analyses. A recent meta-analysis is however in favor of an independent role for triglycerides, particularly in women. Two prospective studies published in 1998 confirmed that hypertriglyceridemia is an independent risk factor. VARIABLE IMPACT: Hypertriglyceridemia is a heterogeneous anomaly, not only due to different underlying pathophysiological mechanisms, but also in terms of cardiovascular risk. In familial hypertriglyceridemia, cardiovascular risk is apparently only moderately affected. Inversely, in combined familial hypertriglyceridemia and hyperapobetalipoproteinemia, the risk of premature cardiovascular disease is increased. ATHEROGENIC EFFECT: Unlike large VLDL rich in triglycerides, small VLDL rich in cholesterol ester have a strong atherogenic potential. Likewise, remnants are potentially atherogenic due to their relatively high cholesterol ester component and their accumulation on the arterial wall (Zilversmit postprandial atherogenesis theory). INCREASED RISK: The triglyceride-related risk is partly the consequence of frequently associated changes in lipoprotein distribution (lower HDL cholesterol, principal consequence of hypertriglyceridemia, elevation of small dense more readily oxidizable LDL) and hemostasis disorders (increased factor VIIc and PAI-1). In addition, hypertriglyceridemia is often found with other cardiovascular risk factors, particularly it readily occurs in insulin resistance syndromes.

Arteriosclerosis↗
PubMed1994

[Hypertriglyceridemia and acute pancreatitis].

Data of 26 patients suffering from severe pancreatitis, who were treated at the anesthesiologic intensive care unit during the years 1991 and 1992, were evaluated with respect to etiologic factors, especially hypertriglyceridemia, stage of the disease and clinical outcome. Hypertriglyceridemia was found in 13 cases (11 men, 2 women, mean age 42 +/- 9 years) with values between 330 mg/dl and 4000 mg/dl. Lipid electrophoresis revealed a pattern typical for type IV hyperlipidemia. Insulin dependent diabetes was present in 4 patients and 5 reported about an unusual high alcohol intake preceding pancreatitis. Beside surgical approaches, including drainage and lavage, and basic intensive care treatment plasmapheresis was performed in 8 patients with hypertriglyceridemia. 5 patients with pancreatitis and hypertriglyceridemia died out of multiorganic failure, and so the mortality rate was 38%. The group of patients with pancreatitis caused by cholelithiasis or chronic alcohol consumption showed a mortality rate of 46%. The poor outcome of pancreatitis associated with hypertriglyceridemia demonstrates the importance of the treatment of hypertriglyceridemia in order to prevent the development of pancreatitis. The determination of plasma triglyceride values should belong to the routine diagnostic procedures in acute pancreatitis.

Acute Disease↗
PubMed1994

Dietary cottonseed protein can reduce the severity of retinoid-induced hypertriglyceridemia.

Hypertriglyceridemia is frequently noted as a side effect when retinoids (e.g., 13-cis-retinoic acid) are used in human chemoprevention trials. Dietary oilseed proteins (e.g., cottonseed and soy protein) are known to reduce the severity of diet-induced hypertriglyceridemia, but their influence on drug-induced hypertriglyceridemia has not been studied previously. In the present study, the ability of dietary cottonseed protein (as cottonseed flour) to prevent drug-induced hypertriglyceridemia was investigated by feeding male Fischer 344 rats diets having casein or cottonseed protein flour with or without 13-cis-retinoic acid. Animals were fed diets for 2 weeks. Retinoid administration was associated with the induction of hypertriglyceridemia and with changes in serum fatty acid profile, the most noticeable being lowered levels of arachidonic acid. Levels of this fatty acid were 35 and 54% of control levels for retinoid-treated animals fed casein and cottonseed flour, respectively. Animals fed cottonseed flour had lower serum triglyceride levels than ones fed casein for both retinoid-containing and control diets. Dietary cottonseed flour had no effect on food intake or body weight and did not affect serum drug levels. Thus, dietary cottonseed protein can reduce the severity of retinoid-induced hypertriglyceridemia without having adverse effects on food intake or growth; in addition, because levels of 13-cis-retinoic are unaffected by cottonseed protein, it is unlikely that the chemopreventive effectiveness of the drug will be compromised by the inclusion of this protein in the diet.

Animals↗
PubMed2003

A novel type hypertriglyceridemia observed in FLS mice.

The unique inborn hypertriglyceridemia seen in FLS (fatty liver Shionogi) mice was relieved by the administration of purified apolipoprotein (apo) C-II. Lipoprotein lipase (LPL) and its cofactor, apoC-II, play a pivotal role in VLDL metabolism. Therefore, we investigated the genetic background involved in this hypertriglyceridemia. Plasma levels of TG and total cholesterol as well as LPL activity were measured in male FLS mice and C57/BL6J mice. Agarose gel electrophoresis and fast protein liquid chromatography were used to analyze the lipoprotein profile. A cross experiment was done to determine the genetic background of hypertriglyceridemia observed in FLS mice. cDNA sequences of apoC-II and apoC-III of FLS mice were determined. Prealpha-lipoprotein was the predominant lipoprotein class in FLS mouse plasma. LPL activity remained in the range observed in C57/BL6J mice, and purified apoC-II transiently relieved FLS mice from hypertriglyceridemia. Prealpha-lipoproteinemia was inherited in an autosomal recessive manner. ApoC-III appeared to be a causal factor for this unique hypertriglyceridemia. Microsatellite analysis, however, revealed that the responsible chromosome was not 7; rather, apoC-III mapped onto chromosome 9. Therefore, we suggest apoC-III as a candidate causative factor for the hypertriglyceridemia observed in FLS mice because an excessive amount of apoC-III attenuates LPL activity in vivo and in vitro.

Animals↗
PubMed1980

Pancreatitis, familial hypertriglyceridemia, and pregnancy.

Interrelationships between pregnancy, hypertriglyceridemia, and pancreatitis were assessed in three women with familial hypertriglyceridemia. One subject had known familial hypertriglyceridemia, familial type V hyperlipoproteinemia, prior to conception. In this woman a progressive increase in triglyceride levels to more than 3,000 mg/dl during the first two trimesters required dietary intervention and hospitalization at 28 weeks' gestation. Use of an isocaloric National Institutes of Health type V diet reduced triglyceride levels to less than 900 mg/dl; the pregnancy was uneventful with term delivery of a healthy neonate. The familial hypertriglyceridemia was covert in the other two women until term. In one subject, subsequently shown to have familial type V, acute hemorrhagic pancreatitis with a pancreatic pseudocyst, shock, and hypocalcemia developed at 39 weeks' gestation; the neonate was safely delivered, and the mother survived. In the second, entirely asymptomatic subject, triglyceride levels greater than 5,000 mg/dl were discovered incidentally at term cesarean section during delivery of a healthy neonate. With a fat restricted diet, plasma triglyceride levels abruptly fell post partum to less than 500 mg/dl, and subsequent studies revealed familial type III hyperlipoproteinemia. Routine quantitation of plasma cholesterol and triglyceride levels or simple visual examination of fasting plasma for triglyceride-induced opacity or "milky" appearance should be done during early pregnancy. This would allow the obstetrician to identify women with severe familial hypertriglyceridemia prior to the superimposition of the physiologic hyperlipidemia of pregnancy upon familial hypertriglyceridemia with resultant, and often catastrophic, acute pancreatitis.

Adult↗
PubMed1987

Borderline fasting hypertriglyceridemia: absence of excess risk of all-cause and cardiovascular disease mortality in healthy men without hypercholesterolemia.

The majority of prospective studies have shown no independent effect of triglyceride on the prediction of cardiovascular disease after the effects of cholesterol and other heart disease risk factors have been accounted for statistically. Because the association of borderline elevation of triglyceride levels (250-499 mg/dl) with cardiovascular risk might be obscured by its strong correlation with hypercholesterolemia, we examined the relationship in healthy men without hypercholesterolemia. In a population sample of 1,589 healthy fasting men ages 30-79 without known cardiovascular disease or categorical hypercholesterolemia, the prevalence of borderline hypertriglyceridemia was 4.2%, and was unrelated to age. There was no significant excess of borderline hypertriglyceridemia in men with systolic hypertension, or in men who reported use of antihypertensive drugs, current cigarette smoking, or a family history of heart attack before or after age 50. Only obesity, a personal history of diabetes, and fasting hyperglycemia were significantly more common in men with borderline hypertriglyceridemia. Moreover, hypertriglyceridemia was a relatively weak marker for those with diabetes or obesity, being present in only 9% of the former and 6% of the latter. A 12-year follow-up of these men showed no significant association of hypertriglyceridemia with all-cause or cardiovascular death either by univariate analysis or after adjusting for risk factors. These data support the conclusion that borderline hypertriglyceridemia is a poor marker for cardiovascular risk in healthy older men without hypercholesterolemia.

Adult↗
PubMed1999

[Primary hypertriglyceridemia].

Familial hypertriglyceridemia has been suggested to be an autosomal dominant condition with age-dependent penetrance, but so far the underlying defective gene has not been elucidated. LPL gene and apolipoprotein A-I/C-III/A-IV gene cluster might be involved in familial clustering of hypertriglyceridemia. Heterozygous LPL deficiencies caused by several types of gene mutation are known to result in a partial defect in catabolism of VLDL, occurring mild to moderate hypertriglyceridemia. However, although the mutation of LPL gene results in reduced lipolytic activity, this type of dyslipidemia appears to manifest only if VLDL-TG production is also increased. These suggest that overproduction of VLDL-TG is a more important cause of hypertriglyceridemia than is the LPL deficiency. Moreover, families with a clustering of hypertriglyceridemia are known to be at increased risk of hyperinsulinemia due to impaired insulin sensitivity. Impaired insulin sensitivity and hyperinsulinemia are the major determinants of excessive VLDL-TG synthesis and dyslipidemia. Taken together, abnormally high production of VLDL-TG seemed to be the major factor in causing familial hypertriglyceridemia, but clearance capacity can play an important role in determining the severity of the TG elevation.

Apolipoprotein C-III↗
PubMed1992

Association of a DNA polymorphism of the apolipoprotein A-I/C-III/A-IV gene cluster with hypertriglyceridemia in obese people.

Hypertriglyceridemia is frequently associated with obesity. In the general Caucasian population, an association of the uncommon S2 allele of a DNA polymorphism of the apolipoprotein (apo) A-I/C-III/A-IV gene cluster with hypertriglyceridemia has been reported. To assess the risk of hypertriglyceridemia associated with the S2 allele in obesity, lipid status and apo A-I/C-III/A-IV genotypes were studied in 90 unrelated Caucasian obese subjects. Age, body mass index, percentage body fat and waist-hip ratio were comparable between genotypes. The frequency of S1/S2 genotype was 35% in the hypertriglyceridemic group versus 11.4% in the normotriglyceridemic group (P < 0.05). The odds ratio of hypertriglyceridemia was 3.7 for obese subjects with the S2 allele and 26.7% of hypertriglyceridemias could be attributed to the S2 allele. Women with the S1/S2 genotype had also significantly higher VLDL- and LDL-cholesterol concentrations. These results suggest that the S2 allele modulates the effects of obesity on lipoproteins and increases the risk of hypertriglyceridemia when obese.

Adult↗
PubMedDate not supplied

[Familial hypertriglyceridemia and diabetes mellitus type 2].

Hypertriglyceridemia is a cardiovascular risk factor in type-2 diabetes. However, this abnormality may be caused by several mechanisms. In familial hypertriglyceridemia, a hyperlipidemia associated with type-2 diabetes, plasma accumulation of non atherogenic particles explains the presence of hypertriglyceridemia. Our objective was to compare the prevalence of coronary insufficiency and carotid artery stenosis in patients with type-2 diabetes with or without familial hypertriglyceridemia. Controls were paired against cases based on age, gender, diabetes duration, treatment and other cardiovascular risk factors. Controls had either a normal lipid profile (n=48) or hyperlipidemia (n=15). The intima-media thickness of the carotid arteries was significantly lower in cases compared to controls (0.55 +/- 0.12 vs 0.63 +/- 0.22 in normolipidemic controls and 0.66 +/- 0.18 mm in hyperlipidemic subjects (p=0.02)). Exercise treadmill testing was abnormal in a similar proportion of cases and controls (4.8 vs 6.2%). Incidence of cardiovascular complications was not different between groups. We therefore conclude that severe hypertriglyceridemia due to familial hypertriglyceridemia is not associated with an increased prevalence of symptomatic atherosclerosis in patients with type-2 diabetes.

Carotid Stenosis↗
PubMed1979

Characterization of a model of dietary-induced hypertriglyceridemia in young, nonobese rats.

Healthy, nonobese, young rats developed hypertriglyceridemia (mean triglyceride levels of 250 mg/dl) following consumption of a sucrose-lard diet. The hypertriglyceridemia was apparent three days after start of the diet and persisted throughout the 4-week experimental period. Body weight, liver weight, and serum glucose levels were similar in animals eating either the sucrose-lard diet or standard rat chow. On the other hand, serum free fatty acid levels were slightly increased and serum insulin levels were substantially increased in animals eating the sucrose-lard diet. Determination of very low density lipoprotein turnover revealed that total triglyceride secretion in rats eating the sucrose-lard diet was significantly (P < 0.01) increased over that of rats eating standard chow. Direct measurement of hepatic and intestinal very low density lipoprotein secretion indicated that the observed rise in total triglyceride secretion was secondary to increased secretion of very low density lipoproteins by the liver. Finally, lipoprotein lipase activity of adipose tissue from rats eating the sucrose-lard diet was equal to, or greater than (depending upon sampling time), the activity of the enzyme from adipose tissue of rats eating the control diet. These data indicate that young, nonobese, rats develop hypertriglyceridemia when they ingest a sucrose-lard diet, and that the rise in plasma triglyceride levels results from an increase in hepatic very low density lipoprotein secretion. The dietary-induced hypertriglyceridemia is associated with elevated serum insulin levels, and, as such, may provide a useful animal model to use in studies aimed at defining the pathogenesis of endogenous hypertriglyceridemia in man.-Reaven, G. M., T. R. Risser, Y-D. I. Chen, and E. P. Reaven. Characterization of a model of dietary-induced hypertriglyceridemia in young, nonobese rats.

Animals↗
PubMed1977

Insulin, obesity, and triglyceride interrelationships in sixteen children with familial hypertriglyceridemia.

Sixteen children with familial hypertriglyceridemia were studied to determine whether there were any distinctive insulintriglycerid-obesity relationships in pediatric familial hypertriglyceridemia. Eleven of 16 children had calculated fat mass greater than the 97th percentile for age, height, and sex. When compared with 16 normal control subjects matched for degree of obesity immunoreactive insulin and glucose response during oral glucose tolerance was similar for normal and hypertriglyceridemic children. By either simple correlation or multiple regression analysis, plasma, triglycerides did not correlate significantly with measurements of insulin or obesity in hypertriglyceridemic or normal children. Within the limits of a small sample size, and in the presence of obesity, insulin does not appear to play a predominant role in the genesis of hypertriglyceridemia in children with familial hypertriglyceridemia. With a small mean weight loss of 1.8 kg and adherence to a diet with 20% of calories as protein, 40% each as fat and carbohydrate, polyunsaturate to saturate ratio of 1.5:1, mean plasma triglycerides were reduced from 238 to 140 mg/100 ml in the 11 obese children with familial hypertriglyceridemia (P less than 0.02). Speculation In spite of the complicating role of obesity, adolescence, and the small sample size, it is interesting to note that the correlation coefficients between triglyceride and insulin/glucose area (0.36), and insulin area (0.30), although not significant (P less than 0.1), were considerably higher in hypertriglyceridemic children than in normal subjects in whom comparable correlation coefficients were 0.08 and 0.08. This infers that the potential role of insulin in triglyceride metabolism in children with familial hypertriglyceridemia might be discerned with longitudinal follow-up into adulthood.

Adolescent↗
PubMed1987

Suppression of hypertriglyceridemia of Ehrlich carcinoma-bearing mice by an antibiotic, ascofuranone.

Ehrlich ascites carcinoma-bearing mice exhibit hypertriglyceridemia. An antitumor antibiotic, ascofuranone, suppressed tumor-induced hypertriglyceridemia when administered i.p. even when no evident antitumor activity was observed without affecting the levels of free fatty acids, phospholipids, cholesterol, glucose, and total protein in plasma. Ascofuranone did not reduce plasma triglycerides of normal mice. Insulin and clofibrate, known modifiers of lipid metabolism, showed no significant suppression. Ascofuranone is also effective on solid tumor-induced hypertriglyceridemia. Another notable change of metabolism affected by tumor-bearing in the early stage where hypertriglyceridemia has not yet fully progressed is hypoglycemia. Although ascofuranone did not affect hypoglycemia, the suppressive effect on hypertriglyceridemia was more evident when ascofuranone was administered in the early stage than in the later stage. These results suggest that ascofuranone suppresses hypertriglyceridemia by specifically affecting the changes of host metabolism which is induced in the early stage of tumor bearing.

Animals↗
PubMed2002

Human immunodeficiency virus genotype and hypertriglyceridemia.

Many HIV patients develop a progressive syndrome of abnormal body fat distribution accompanied by hypertriglyceridemia. Antiretroviral agents are thought to be etiologic in the syndrome, often termed "highly active antiretroviral therapy (HAART)-associated lipodystrophy." In the course of clinical HIV genotype testing, we observed that our HIV patients with hypertriglyceridemia had viral genotypes that were more highly mutated than those of our therapy-matched control patients. Hypertriglyceridemia was statistically associated with predicted resistance for three nucleoside reverse transcriptase inhibitors: zidovudine, abacavir, and stavudine. Statistical analysis of 51 patients in retrospect revealed a strong association of mutations at reverse transcriptase codons M41 and T215 with hypertriglyceridemia (chi-square (chi(2)) = 8.375, P=.0038; and chi(2)=7.445, P=.0064, respectively). This was in contrast to silent mutations, which occurred at equivalent rates in retroviral genotypes of patients with and without hypertriglyceridemia. The findings imply that the HIV genotype itself may be a significant etiologic factor in antiretroviral-associated lipodystrophy.

Adult↗
PubMed1995

Dietary rat models in which the development of hypertriglyceridemia and that of insulin resistance are dissociated.

The consequences of chronic ingestion of a high-carbohydrate (starch + glucose [HCHO]) and high-fat (lard + corn oil [HFAT]) diet on triglyceride metabolism and insulin sensitivity were evaluated in fasted and fed rats. Compared with their HFAT counterparts, animals fed the HCHO diet displayed fasting and postprandial hypertriglyceridemia that was apparent after 3 weeks of feeding and persisted after 6 weeks. It was determined that hypertriglyceridemia was due to oversecretion of triglycerides into the circulation. During fasting triglyceride accumulation in plasma after administration of Triton WR1339 was indeed twofold higher in HCHO than in HFAT rats, whereas the global capacity for intravascular triglyceride hydrolysis, as assessed by an intravenous fat tolerance test and measurement of postheparin plasma lipoprotein and hepatic lipase activities, was comparable in both dietary cohorts. The postprandial increase in triglycerides after a high-carbohydrate meal was larger in HCHO than in HFAT rats. A fasting intravenous glucose tolerance test (IVGTT) showed that HFAT animals displayed insulin resistance after 3 weeks of feeding, which worsened after 6 weeks of treatment. Thus, the HCHO diet elicited fasting and postprandial hypertriglyceridemia without impairment of insulin sensitivity as compared with the HFAT diet, whereas the latter brought about deterioration of the sensitivity of glucose metabolism to insulin without affecting triglyceridemia. From these studies and other animal models, it is suggested that rapid delivery of fatty acids to tissues from chylomicron-derived triglycerides leads to insulin insensitivity, while fatty acids may not be available to increase endogenous production of triglycerides because they are mainly oxidized. In contrast, dietary starch/glucose increases hepatic synthesis and secretion of triglycerides that result in hypertriglyceridemia, but the deleterious effects of glucose-fatty acid competition on insulin sensitivity are prevented because endogenously derived triglycerides are catabolized more slowly and glucose is available for oxidation. The present results support the concept that coexistence of hypertriglyceridemia and resistance of glucose metabolism to insulin may be frequent but not obligatory.

Animals↗
PubMed1998

Hypertriglyceridemia, atherogenic dyslipidemia, and the metabolic syndrome.

The importance of high serum cholesterol, especially a high level of low-density lipoprotein (LDL) cholesterol, as a risk factor for coronary artery disease is well established. Likewise, efficacy for decreasing risk for coronary artery disease by LDL-lowering therapy has recently been documented through clinical trials. However, many high-risk patients manifest elevated serum triglyceride levels, and the role of hypertriglyceridemia in causation of coronary artery disease remains to be elucidated. Nonetheless, there is growing evidence that hypertriglyceridemia is a marker for increased risk for coronary artery disease; in fact, it can serve as a marker for several atherogenic factors. These factors include increased concentrations of atherogenic triglyceride-rich lipoproteins; the atherogenic lipoprotein phenotype, or lipid triad; and the metabolic syndrome. The lipid triad consists of elevated serum triglycerides, small LDL particles, and low high-density lipoprotein (HDL) cholesterol. The metabolic syndrome includes the coexistence of the lipid triad, elevated blood pressure, insulin resistance (plus glucose intolerance), and a prothrombotic state. Many previous studies indicate that hypertriglyceridemia is strongly associated with all of these atherogenic factors. The clinical approach to treatment of patients with hypertriglyceridemia thus requires a broad-based strategy that includes reduction of atherogenic triglyceride-rich lipoproteins, reversal of the lipid triad, and favorable modification of the metabolic syndrome. The development of therapeutic regimens to effect these changes poses a challenge for future research on the problem of hypertriglyceridemia.

Animals↗