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PubMed1999

[Comparison of LDL-C values measured with the automated method and the ultracentrifugation method in severe hypertriglyceridemia, and prevalence and life-style of patients with hypertriglyceridemia].

The correlation between LDL-cholesterol (LDL-C) values assayed by the direct method and the ultra-centrifugation method is reported good in normal to moderate hypertriglyceridemia, but it is not clear in severe hypertriglyceridemia. We examined such a correlation in mild (triglycerides, 150-400 mg/dl; n = 3) and severe (> or = 800 mg/dl, n = 9) hypertriglyceridemia. The bias of LDL-C determined by the direct method in comparison with the ultracentrifugation method was from -1.1% to 3.4% and from -49.5% to 15.7% in mild and severe hypertriglyceridemia, respectively. The prevalence of severe hypertriglyceridemia was only 0.2% both in hospital patients and in company workers. Data analyses of company workers indicated that people with severe hypertriglyceridemia have a higher body-mass index, consume more alcohol, smoke more, and exercise less than those with a normal level of triglycerides. These results suggest that there is not a good correlation between LDL-C values assayed by the direct method and the ultracentrifugation method in severe hypertriglyceridemia; but that the direct method can be used for the clinical examination of LDL-C, because of the very low prevalence of severe hypertriglyceridemia. Patients with severe hypertriglyceridemia should improve their life-style as soon as possible.

Adult↗
PubMed2003

An observational study of severe hypertriglyceridemia, hypertriglyceridemic acute pancreatitis, and failure of triglyceride-lowering therapy when estrogens are given to women with and without familial hypertriglyceridemia.

BACKGROUND: We assessed severe hypertriglyceridemia, hypertriglyceridemic acute pancreatitis, and failure of triglyceride-lowering therapy when estrogens were given to 56 women with and without familial hypertriglyceridemia. The 56 women had been consecutively referred to our center over a 3-year period because of triglycerides >400 mg/dl despite diet-drug treatment and/or a history of hypertriglyceridemic acute pancreatitis (AP). Of the 56 women, 17 had received estrogen replacement therapy (ERT), hormone replacement (HRT, n=6), or selective estrogen receptor modulators (SERM, n=1). METHODS: After study at entry, in 56 women (median age, 52 years), 36 with familial hypertriglyceridemia, to lower triglycerides, estrogens and SERMs (hormone treatment, HT) were stopped; a very low fat diet (<15% of calories), gemfibrozil (1.2-1.5 mg/day), and omega-3-fatty acid (4-12 g/day) were started, with restudy 2-4 weeks later. RESULTS: Of the 56 women, 24 (43%) were taking HT at entry, with median fasting triglycerides 1270 mg/dl in the HT group and 1087 mg/dl in the no-HT group. Seventeen women (30%) had a history of AP, nine of whom (53%) were/had been on HT at the development of AP. Significant positive correlates of triglycerides at entry in a stepwise regression model were hemoglobin A(1C) (partial r(2)=10.7%, p<0.05) and an interaction between estrogen use and familial hypertriglyceridemia (partial r(2)=15%, p=0.017). After 2-4 weeks on therapy, median triglycerides in the previous-HT group fell from 1270 to 284 mg/dl (p<0.0001) and in the no-HT group from 1087 to 326 mg/dl (p<0.0001). CONCLUSIONS: Before starting HT, to avoid HT induced hypertriglyceridemic AP and exacerbation of overt or covert familial hypertriglyceridemia, triglycerides must be measured. HT is contraindicated in women with preexisting hypertriglyceridemia (triglycerides> or =500 mg/dl). Triglyceride-lowering diets and drugs often fail in the presence of HT and/or poorly controlled diabetes mellitus, but commonly succeed when HT is stopped and diabetes mellitus is tightly controlled.

Adult↗
PubMed1995

Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes.

Lipoprotein lipase (LPL)-deficient mice have been created by gene targeting in embryonic stem cells. At birth, homozygous knockout pups have threefold higher triglycerides and sevenfold higher VLDL cholesterol levels than controls. When permitted to suckle, LPL-deficient mice become pale, then cyanotic, and finally die at approximately 18 h of age. Before death, triglyceride levels are severely elevated (15,087 +/- 3,805 vs 188 +/- 71 mg/dl in controls). Capillaries in tissues of homozygous knockout mice are engorged with chylomicrons. This is especially significant in the lung where marginated chylomicrons prevent red cell contact with the endothelium, a phenomenon which is presumably the cause of cyanosis and death in these mice. Homozygous knockout mice also have diminished adipose tissue stores as well as decreased intracellular fat droplets. By crossbreeding with transgenic mice expressing human LPL driven by a muscle-specific promoter, mouse lines were generated that express LPL exclusively in muscle but not in any other tissue. This tissue-specific LPL expression rescued the LPL knockout mice and normalized their lipoprotein pattern. This supports the contention that hypertriglyceridemia caused the death of these mice and that LPL expression in a single tissue was sufficient for rescue. Heterozygous LPL knockout mice survive to adulthood and have mild hypertriglyceridemia, with 1.5-2-fold elevated triglyceride levels compared with controls in both the fed and fasted states on chow, Western-type, or 10% sucrose diets. In vivo turnover studies revealed that heterozygous knockout mice had impaired VLDL clearance (fractional catabolic rate) but no increase in transport rate. In summary, total LPL deficiency in the mouse prevents triglyceride removal from plasma, causing death in the neonatal period, and expression of LPL in a single tissue alleviates this problem. Furthermore, half-normal levels of LPL cause a decrease in VLDL fractional catabolic rate and mild hypertriglyceridemia, implying that partial LPL deficiency has physiological consequences.

Adipose Tissue↗
PubMed1987

Bile acid metabolism in hereditary forms of hypertriglyceridemia: evidence for an increased synthesis rate in monogenic familial hypertriglyceridemia.

This study was undertaken to characterize bile acid metabolism in hereditary forms of hypertriglyceridemia. Ten hypertriglyceridemic patients (type IV phenotype) with familial combined hyperlipidemia and 7 patients with monogenic familial hypertriglyceridemia (FHTG) were compared with 18 healthy controls; all subjects were males. Pool size, synthesis rate, and fractional catabolic rate of cholic and chenodeoxycholic acids were determined with an isotope dilution technique. Patients with FHTG had synthesis rates of cholic acid, chenodeoxycholic acid, and total bile acids above those seen in normal controls (P less than 0.001); also the fractional catabolic rates of both bile acids were increased (P less than 0.001). In contrast, bile acid kinetic parameters were--with one exception--within normal limits in patients with familial combined hyperlipidemia. The abnormality of bile acid metabolism could also be identified in a normolipidemic individual presumed to carry the gene for FHTG. The postprandial rise of serum bile acids was blunted in FHTG, indicating that the intestinal uptake of bile acids may be deficient in this condition. We conclude that FHTG, but not familial combined hyperlipidemia, is frequently associated with a defective regulation of bile acid synthesis, resulting in abnormally high production rate of bile acids. It is hypothesized that this abnormality is important for the subsequent development of hypertriglyceridemia.

Adult↗
PubMed2002

Insulin resistance but not hypertriglyceridemia per se is associated with endothelial dysfunction in chronic hypertriglyceridemia.

OBJECTIVES: To infer the relative impact of elevated triglyceride levels and insulin resistance on endothelial dysfunction in patients with chronic hypertriglyceridemia (HTG). METHODS: Endothelial function was studied in 11 HTG patients and 16 normolipidemic controls. Cumulative-dose infusions of 5-hydroxytryptamine (5HT) and sodium nitroprusside were infused locally into the brachial artery to study endothelium-dependent and endothelium-independent vasodilation, respectively. Data of the HTG patients were dichotomized around the median of insulin resistance, calculated as HOMA-index, forming HTG groups with mild (HTG-MIR) and severe insulin resistance (HTG-SIR). RESULTS: HTG patients had higher triglyceride levels and smaller LDL particle size than controls (both P< or =0.001), whereas these parameters did not differ between both HTG groups. Insulin resistance was higher in both HTG groups than in controls (11.1 (7.0-14.5) and 4.9 (4.0-6.7) vs. 2.4 (4.9-5.2), respectively, both P<0.001). Similarly, free fatty acid levels, another indicator of insulin resistance, were highest in the HTG-SIR group, followed by those in the HTG-MIR and control group (0.7 (0.6-0.8), 0.5 (0.4-0.6) and 0.4 (0.3-0.4) mmol/l, respectively, all P<0.05). Endothelial-dependent vasodilation was similar in HTG-MIR and controls. In contrast, the response to 5HT was attenuated in the HTG-SIR group compared to controls (low and high dose by, respectively, -60 and -44%, both P<0.01), and tended to be lower than in the HTG-MIR group (-43%, P=0.068 and -41%, P=0.100, respectively). Endothelium-independent vasodilation did not differ between the three groups. CONCLUSION: These findings indicate that chronic hypertriglyceridemia per se is not associated with endothelial dysfunction. In contrast, the presence of insulin resistance, characterized by hyperinsulinemia and FFA elevation, contributes to the induction of endothelial dysfunction in chronic HTG.

Adult↗
PubMed1992

[Diet and hypertriglyceridemia: influence of dietary modifications on plasma lipids, lipoproteins and apoproteins in patients with primary hypertriglyceridemia].

BACKGROUND: To investigate the influence of dietary changes on plasma lipoproteins and apoproteins in 10 patients with hypertriglyceridemia (plasma triglycerides greater than 1000 mg/dl). METHODS: A sequential study with three periods was designed: 1) Inclusion with uncontrolled free diet; 2) Two weeks of a diet with about 1000 calories/day, controlled with a daily survey; and 3) One week of "free" diet of about 2000 calories. At the end of the three periods the following were measured in each patient: weight, glycemia, plasma IRI and C-peptide, plasma, triglycerides, cholesterol, chylomicron, VLDL, LDL and HDL cholesterol. At the end of the second and third periods the caloric and immediate principles intake were individually considered. RESULTS: A reduction in plasma cholesterol and triglycerides was observed in all cases after the caloric reduction, and also a disappearance of chylomicrons. The reduction of triglycerides took place in all lipoproteins. By contrast, after the low-calorie diet only the VLDL-cholesterol was reduced, while LDL- and HDL-cholesterol increased. The apo C-III/apo C-II ratio was significantly reduced after the low-calorie diet. The plasma glycemia, IRI and C-peptide were negatively correlated with LDL-cholesterol and with the apo C-III/apo C-II ratio. The best model to explain the oscillations of plasma triglycerides depending on the diet was that including the three ingested immediate principles together with the total diet calories. CONCLUSIONS: During the caloric restriction there would be an increased catabolism of VLDL to LDL. This reduction would be mediated by C-III and C-II apoproteins, probably through the oscillations of plasma IRI.

Apolipoproteins↗
PubMed2005

Propofol-associated hypertriglyceridemia and pancreatitis in the intensive care unit: an analysis of frequency and risk factors.

STUDY OBJECTIVES: To characterize the frequency, severity, risk factors, and clinician response to propofol-associated hypertriglyceridemia and hypertriglyceridemia-associated pancreatitis. DESIGN: Retrospective analysis. SETTING: Medical and surgical intensive care units. PATIENTS: One hundred fifty-nine adult intensive care patients administered propofol for 24 hours or longer and who had at least one serum triglyceride concentration. MEASUREMENTS AND MAIN RESULTS: Patient records were reviewed to identify the frequency of hypertriglyceridemia (serum triglyceride concentration > or = 400 mg/dl) and pancreatitis (amylase concentration > or = 125 IU/L, lipase concentration > or = 60 IU/L, and abdominal computed tomography scan or clinical examination findings consistent with pancreatitis). Of the 159 patients, 29 (18%) developed hypertriglyceridemia; six (21%) of the 29 had a serum triglyceride concentration of 1000 mg/dl or greater. The median maximum serum triglyceride concentration was 696 mg/dl (range 403-1737 mg/dl). At the time when hypertriglyceridemia was detected, the median infusion rate of propofol was 50 microg/kg/minute (range 5-110 microg/kg/min). The median time from the start of propofol therapy to identification of hypertriglyceridemia was 54 hours (range 14-319 hrs). Propofol was discontinued within 24 hours of detecting the hypertriglyceridemia 84% of the time. Compared with those who did not develop hypertriglyceridemia, patients who developed hypertriglyceridemia were older, had a longer intensive care unit stay, and received propofol for a longer duration; they were also more likely to be admitted to the medical versus the surgical intensive care unit. Pancreatitis developed in three (10%) of the 29 patients with hypertriglyceridemia. CONCLUSION: Hypertriglyceridemia and hypertriglyceridemia-associated pancreatitis are often seen in intensive care patients receiving propofol. Serum triglyceride concentrations should be routinely monitored in these patients. In addition, alternative sedation strategies should be considered when hypertriglyceridemia is detected.

Acute Disease↗
PubMed1983

Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia.

Plasma lipoprotein concentration, composition, and size were evaluated in two common familial forms of hypertriglyceridemia and compared with those in normal subjects. The very low density lipoproteins (VLDL) were triglyceride-enriched in familial hypertriglyceridemia (triglyceride/apoprotein B ratio: 25.7 +/- 8.9) as compared to normal (9.6 +/- 12.2, P < 0.001) or familial combined hyperlipidemia (9.7 +/- 3.3, P < 0.001). The diameter of VLDL was larger in familial hypertriglyceridemia (3.27 +/- 0.28 pm) than in familial combined hyperlipidemia (2.87 +/- 0.16 pm, P < 0.02). Although in familial hypertriglyceridemia VLDL tended to be larger, and in familial combined hyperlipidemia VLDL tended to be smaller than normal (3.08 +/- 0.48 pm), neither of these differences were significant. While VLDL was normally distributed in the control population, the size was skewed to larger particles in familial hypertriglyceridemia with fewer small particles (P < 0.05) and skewed to smaller particles in familial combined hyperlipidemia with fewer large particles (P < 0.05). VLDL was reciprocally related to low density lipoproteins (LDL) in familial combined hyperlipidemia (r = -0.80 to -0.87) suggesting that the concentrations of these individual lipoprotein groups were somehow interrelated. There was no significant relationship between these two lipoprotein classes in familial hypertriglyceridemia or in normals. In familial combined hyperlipidemia, the apoprotein A-I/A-II ratio was below normal (P < 0.01) suggestive of low HDL(2) levels. This change in apoprotein composition was independent of VLDL or LDL concentration. In familial hypertriglyceridemia, high density lipoprotein (HDL) cholesterol was reduced (33% below mean normal) and HDL triglyceride was increased (by 46%), while the concentration of apoA-I and apoA-II was normal. VLDL triglyceride was inversely related to HDL cholesterol in familial hypertriglyceridemia (r = -0.74, P < 0.005), but not in familial combined hyperlipidemia. The large, triglyceride-enriched VLDL observed in familial hypertriglyceridemia is compatible with the reported increase in VLDL triglyceride synthesis seen in this disorder. The increase in VLDL apoprotein B synthesis previously reported in familial combined hyperlipidemia was associated with VLDL of normal composition. The changes in HDL cholesterol in these two disorders might reflect exchange of triglyceride between VLDL and HDL or could be related to transfer of surface components during the catabolism of VLDL. The reciprocal relationship between various components of VLDL and LDL seen in familial combined hyperlipidemia, but not in familial hypertriglyceridemia or in normal subjects, might provide some insight into the pathological abnormalities in these disorders. The differences between these two common familial forms of hypertriglyceridemia provide further support that they are distinct entities.-Brunzell, J. D., J. J. Albers, A. Chait, S. M. Grundy, E. Groszek, and G. B. McDonald. Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia.

Adult↗
PubMedDate not supplied

Hypertriglyceridemia.

Hypertriglyceridemia is a commonly encountered lipid abnormality frequently associated with other lipid and metabolic derangements. The National Cholesterol Education Program recommends obtaining a fasting lipid panel in adults over the age of 20. The discovery of hypertriglyceridemia should prompt an investigation for secondary causes such as high fat diet, excessive alcohol intake, certain medications, and medical conditions (eg, diabetes mellitus, hypothyroidism). In addition, patients should be evaluated for other components of the metabolic syndrome. These include abdominal obesity, insulin resistance, low high-density lipoprotein (HDL), high triglyceride, and hypertension. Hypertriglyceridemia is classified as primary hypertriglyceridemia when there are no secondary causes identified. Primary hypertriglyceridemia is the result of various genetic defects leading to disordered triglyceride metabolism. It is important to treat hypertriglyceridemia to prevent pancreatitis by reducing triglyceride levels to <500 mg/dL. Furthermore, lowering triglycerides while treating other dyslipidemias and components of the metabolic syndrome will reduce coronary events. However, it is controversial how much isolated hypertriglyceridemia correlates directly with coronary artery disease and further studies are needed to clarify whether treatment for this condition leads to meaningful clinical outcomes. Therapeutic lifestyle changes (TLC) are the first line of treatment for hypertriglyceridemia. These changes include a low saturated fat, carbohydrate-controlled diet, combined with alcohol reduction, smoking cessation, and regular aerobic exercise. High doses of omega-3 fatty acids from fish and fish oil supplements will lower triglyceride levels significantly. When patients do not reach their goals by TLC, drug therapy should be started. In cases of isolated hypertriglyceridemia, fibrates are initially considered. When elevated low-density lipoprotein levels accompany hypertriglyceridemia, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are preferred. In patients with low HDL levels and hypertriglyceridemia, extended release niacin can be considered. A combination of the medicines may be necessary in recalcitrant cases.

Adult↗
PubMed1996

Retinoid-induced hypertriglyceridemia in rats is mediated by retinoic acid receptors.

Retinoids in clinical use today are known to induce hypertriglyceridemia as one of their major side effects. The purpose of the present study was to determine, in an appropriate animal model, if retinoid-induced hypertriglyceridemia is mediated by retinoic acid receptors (RARs) and/or by retinoid X receptors (RXRs). Oral gavage of male Fischer rats with 13-cis-retinoic acid for 6 days caused a rapid and sustained increase in serum triglycerides that was reversible within 4 days posttreatment. In subsequent experiments, rats were treated by gavage once daily for 3 days with various retinoids, and serum triglyceride levels were determined 24 hr after the last treatment without fasting. All-trans- and 13-cis-retinoic acid, which can be converted to both RAR and RXR agonists, and 9-cis-retinoic acid, an RAR/RXR pan-agonist, caused dose-dependent increases in serum triglycerides at doses that did not cause weight loss or mucocutaneous toxicity. Ro 13-6298 and AGN 190121, two RAR-specific agonists, caused dose-dependent increases in serum triglycerides, although Ro 13-6298 only induced hypertriglyceridemia at weight-suppressive doses. Two RXR-selective agonists, LG100268 and AGN 191701, failed to induce hypertriglyceridemia or weight loss up to the highest doses tested. A structural isomer of AGN 190121 that does not activate RARs or RXRs, AGN 190727, did not induce hypertriglyceridemia. Hypertriglyceridemia induced by AGN 190121 was significantly inhibited by cotreatment with an RAR-selective antagonist, AGN 193109. Taken together, these data provide strong evidence that retinoid-induced hypertriglyceridemia is mediated, at least in part, by RARs. These data also suggest that RXR-specific agonists may have reduced potential to induce hypertriglyceridemia relative to RAR-active retinoids.

Animals↗
PubMed1994

Cutaneous blood flow abnormalities in hypertriglyceridemia.

An accelerated atherosclerosis, in particular of the coronary arteries, was documented in hypertriglyceridemia. The objective of the present study was to assess the cutaneous dynamic blood flow in hypertriglyceridemia, utilizing the optical noninvasive method of laser Doppler flowmetry. The cutaneous blood flow on the forearms was measured during the postischemic reactive hyperemia test in treated and non-treated patients with hypertriglyceridemia and healthy control subjects. The subjects were 32 patients with hypertriglyceridemia--15 untreated and 17 following 6-9 months of bezafibrate treatment--and 27 healthy control subjects. In untreated patients with hypertriglyceridemia, the peak flow was significantly lower than in both the treated group (p < 0.005) and control group (p < 0.02). Similarly, the area under the response-time curve of the untreated patients with hypertriglyceridemia was smaller (p < 0.01 and p < 0.05, respectively). These parameters were similar in the treated group and the control group. The reaction was faster in the treated group, as compared to the other two groups (p < 0.001). The control group exhibited a longer time to decay than the treated group (p < 0.01). Postischemic reactive hyperemia tests in patients with hypertriglyceridemia reveal cutaneous microcirculatory changes in the forearm. These changes may arise from several mechanisms, including functional abnormalities of the endothelium or vascular smooth muscle, or structural changes in the blood vessels that limit vasodilatation. These changes are reversible, and corrected when reducing the triglyceride levels, but other abnormalities are then present, suggesting a permanent damage. These dynamic measurements of cutaneous blood flow are sensitive indicators of atherogenesis, and can be employed for the evaluation of microvascular involvement and follow-up of patients with hypertriglyceridemia.

Arteriosclerosis↗
PubMed1991

Hypertriglyceridemia in diabetes. An approach to management.

Hypertriglyceridemia is not a common finding in well controlled patients with insulin dependent diabetes; however, in noninsulin dependent, or Type II diabetes, hypertriglyceridemia and coronary heart disease are a well recognized clinical triad. In the latter setting, hypertriglyceridemia is usually the result of an associated inherited hyperlipidemia, most commonly familial hypertriglyceridemia but also familial combined hyperlipidemia. In the former, one sees elevated triglycerides and a low HDL-cholesterol, in the latter the same phenotype may be present but often there is a high LDL-cholesterol. Irrespective of the pathogenesis of the primary hypertriglyceridemic disorder, the occurrence of poorly controlled diabetes will enhance the hypertriglyceridemia and even in the Type II diabetic, with triglycerides in the thousands, dietary and glycemic control, alone, will strikingly ameliorate the hypertriglyceridemia. In contrast to patients with hypercholesterolemia, no national guidelines have been proposed for the treatment of patients with hypertriglyceridemia. Yet both experimental and clinical data support an algorithm in which dietary and glycemic control are optimized with a resultant major improvement in triglycerides, followed by the introduction of drug therapy. Three agents are particularly useful in correcting the hypertriglyceridemia: gemfibrozil, niacin, and fish oils, with the first two having the added benefit of increasing HDL levels. Lovastatin is also useful in treating these patients, but primarily for lowering LDL-cholesterol while triglycerides are independently being brought under control. Correction of hyperlipidemia in diabetic patients can generally be achieved with judicious use of dietary, glycemic and drug therapy; however, maintenance of a favorable response requires a high level of patient compliance, which is usually difficult to sustain.

Diabetes Complications↗
PubMed1992

Effects of intralipid-induced hypertriglyceridemia on plasma high-density lipoprotein metabolism in the cynomolgus monkey.

Low plasma levels of high-density lipoprotein (HDL) and apolipoprotein (apo) A-I often accompany human hypertriglyceridemia. In an animal model of hypertriglyceridemia, the lipoprotein lipase (LPL)-inhibited cynomolgus monkey, we reported that plasma levels of apo A-I were decreased and the fractional catabolic rate (FCR) of HDL apo was increased. To explore whether hypertriglyceridemia alone would alter plasma apo A-I levels and catabolism, hypertriglyceridemia was produced by intravenous (IV) infusion of 20% Intralipid into female cynomolgus monkeys. Baseline plasma triglyceride (TG) levels averaged 106 mg/dL. With infusion of 200 mg/kg/h Intralipid TG, plasma TG levels peaked at 967 mg/dL (range, 413 to 1,069; n = 6). More prolonged or more severe hypertriglyceridemia caused serious complications in several monkeys. Despite the severe hypertriglyceridemia, HDL TG content, HDL apoproteins, and plasma apo A-I levels did not markedly change, suggesting that very little HDL remodeling had occurred. Kinetic studies of HDL protein and apo A-I were performed in four pairs of monkeys. The two tracers were removed from the plasma at identical rates. In five pairs of animals, apo A-I turnover during control and Intralipid-induced hypertriglyceridemia was not significantly different. We hypothesize that apo A-I FCR is a function of HDL composition. Because Intralipid infusion did not alter HDL composition to the same degree as did LPL inhibition, its effects on HDL apo catabolism were not apparent.

Animals↗
PubMed1994

Alpha-adrenergic receptors mediate the hypertriglyceridemia induced by endotoxin, but not tumor necrosis factor, in rats.

We assessed the role of catecholamines in mediating the hypertriglyceridemia induced by lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF alpha) in rats by employing specific adrenoreceptor antagonists. Pretreatment with phentolamine, an alpha-antagonist, but not propranolol, a beta-antagonist, suppressed the hypertriglyceridemia induced by either low dose LPS (100 ng/100 g BW) or high dose LPS (50 micrograms/100 g BW). Prazosin, an alpha 1-selective antagonist, significantly suppressed the low dose LPS-induced hypertriglyceridemia by inhibiting hepatic triglyceride secretion, but did not affect the increase in lipolysis. In contrast, yohimbine, an alpha 2-selective antagonist, partially suppressed the high dose LPS-induced hypertriglyceridemia by inhibiting the decrease in postheparin lipoprotein lipase activity. Treatment with phentolamine and propranolol did not affect the hypertriglyceridemia induced by TNF alpha. In summary, these findings suggest that catecholamines via alpha-adrenergic, but not beta-adrenergic, receptors are mediators of the hypertriglyceridemia induced by either low or high dose LPS in rats. alpha 1-Adrenergic receptors are involved in mediating the increased hepatic triglyceride secretion induced by low dose LPS, whereas alpha 2-adrenergic receptors are involved in mediating the decrease in lipoprotein lipase activity induced by high dose LPS. The hypertriglyceridemia induced by either low or high dose LPS may be regulated by a mechanism unrelated to TNF alpha in rats.

Adrenergic alpha-Antagonists↗
PubMed1987

DNA polymorphisms of apolipoprotein A-I/C-III and insulin genes in familial hypertriglyceridemia and coronary heart disease.

Two DNA polymorphisms adjacent to the apolipoprotein A-I/C-III and insulin genes have been suggested to be associated with hypertriglyceridemia and increased risk of coronary heart disease. Using cloned apolipoprotein A-I and insulin gene probes, we determined the genotypes of 39 subjects from six different kindreds with familial clustering of hypertriglyceridemia, 20 additional unrelated subjects with hypertriglyceridemia, 39 patients with angiographically confirmed coronary heart disease (CHD) and 61 normolipemic control subjects. The S2 allele bearing an additional SstI restriction site in the apo A-I/C-III complex was found in 16% of healthy controls, 23% of patients with CHD and 62% (P less than 0.001 when compared to controls) of unrelated subjects with hypertriglyceridemia. Among CHD patients the S2 allele was present in 6 out of 14 hypertriglyceridemic patients but only 3 out of 25 normotriglyceridemic patients (P less than 0.05). The S2 allele was present in 64% of subjects from kindreds with hypertriglyceridemia but this allele did not determine the occurrence of hyperlipidemia. The frequencies of the large size or U allele of the polymorphic DNA region flanking the 5' end of the insulin gene in CHD patients (33%) and in controls (24%) were not significantly different. Neither of the polymorphisms studied was associated with changes in serum LDL or HDL cholesterol levels in patients with CHD or unrelated subjects with hypertriglyceridemia. The data suggest that, at least in the Finnish population, the S2 allele of the apolipoprotein A-I/C-III gene complex may serve as a genetic marker for hypertriglyceridemia, whereas both DNA polymorphisms studied are probably useless in determining individual risks of atherosclerosis.

Adult↗
PubMed1975

Evidence for diabetes mellitus and genetic forms of hypertriglyceridemia as independent entities.

Among 91 index cases whose diagnosis of a genetic type of hypertriglyceridemia was based on family studies, 27% had diabetes. To determine whether the familial forms of hypertriglyceridemia and genetic diabetes mellitus are inherited together or independently, the adult first degree relatives of these propositi were investigated for the presence of diabetes. Frequency of diabetes in first degree relatives of the 25 diabetic patients with a familial form of hypertriglyceridemia was identical whether such relatives were hyperlipidemic or not (13% versus 14.7%). The frequency of diabetes in both the hyperlipidemic and normolipidemic relatives of the 66 nondiabetic hypertriglyceridemic index cases also was not significantly different from each other (6.2% versus 4.0%). These results indicate that while diabetes is frequently associated with hypertriglyceridemia, genetic hypertriglyceridemia, per se, does not carry an increased risk of diabetes. Following treatment of diabetes, elevated triglyceride levels in index cases with both familial hypertriglyceridemia and untreated diabetes returned to lower but still elevated levels resembling those of affected (hypertriglyceridemic) relatives. Thus, the interaction of untreated diabetes and a familial form of hypertriglyceridemia determines the level of plasma triglyceride in a patient with both disorders.

Adult↗
PubMedDate not supplied

Hypertriglyceridemia: a review beyond low-density lipoprotein.

Hypertriglyceridemia is made up of a complex array of dyslipidemias. Difficulties in establishing the independent predictive value of elevated triglycerides in coronary artery disease arise because the triglyceride-rich lipoprotein particles that accumulate are diverse, with differential atherogenic potential, and because hypertriglyceridemia states are typically associated with low high-density lipoprotein cholesterol. When high-density lipoprotein cholesterol is considered in multivariate analysis of the role of hypertriglyceridemia in coronary artery disease, the importance of elevated triglycerides pales, emerging as a statistical second fiddle. However, recent data have affirmed the primary role of triglycerides in the genesis of atherosclerosis. This process involves the overabundance of triglyceride-rich lipoprotein particles, which, paradoxically, can be enriched with cholesterol through the action of cholesterol ester transfer protein. These particles appear to be especially atherogenic. Also, low-density lipoproteins become smaller and denser-small, dense phenotype or pattern B-in hypertriglyceridemia states. This profile is associated with a threefold increase in coronary artery disease risk and is not evident on routine lipid testing. Aggressive management of hypertriglyceridemia requires more detailed lipid analyses to identify patients at risk. In treating hypertriglyceridemia, a risk factor beyond low-density lipoprotein would allow a broader definition of patients at risk for coronary artery disease so that more people would benefit from lipid-lowering initiatives.

Cholesterol↗
PubMed2005

LDL receptor deficiency or apoE mutations prevent remnant clearance and induce hypertriglyceridemia in mice.

We have used adenovirus-mediated gene transfer and bolus injection of purified apolipoprotein E (apoE) in mice to determine the contribution of LDL receptor family members in the clearance of apoE-containing lipoproteins in vivo and the factors that trigger hypertriglyceridemia. A low dose [5 x 10(8) plaque-forming units (pfu)] of an adenovirus expressing apoE4 did not normalize plasma cholesterol levels of apolipoprotein E-deficient (apoE(-/-)) x low density lipoprotein receptor-deficient (LDLr(-/-)) mice and induced hypertriglyceridemia. A similar phenotype of combined dyslipidemia was induced in apoE(-/-) or apoE(-/-) x LDLr(-/-) mice after infection with a low dose (4 x 10(8) pfu) of an adenovirus expressing the apoE4[R142V/R145V] mutant previously shown to be defective in receptor binding. In contrast, a low dose of 5 x 10(8) pfu of the apoE4-expressing adenovirus corrected hypercholesterolemia in apoE(-/-) mice and did not trigger hypertriglyceridemia. Bolus injection of purified apoE in apoE(-/-) x LDLr(-/-) mice did not clear plasma cholesterol levels and induced mild hypertriglyceridemia. In contrast, similar injection of apoE in apoE(-/-) mice cleared plasma cholesterol and caused transiently mild hypertriglyceridemia. These findings suggest that a) the LDL receptor alone can account for the clearance of apoE-containing lipoproteins in mice, and the contribution of other receptors is minimal, and b) defects in either the LDL receptor or in apoE that affect its interactions with the LDL receptor, increase the sensitivity to apoE-induced hypertriglyceridemia in mice.

Animals↗