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PubMed2001

Triglycerides: risk factor or fellow traveler?

An unresolved issue in preventive cardiology is whether the serum triglyceride level is an independent risk factor for coronary heart disease and, as a direct practical consequence, whether it has value as a diagnostic test. Evidence published in the past year has contributed substantially to clarifying these issues. In this review, we discuss the data that bears upon the importance of triglycerides as a risk factor and the implications of recent clinical trials directed at lipid lowering. We then discuss the alternatives for triglyceride lowering therapy in the light of this new knowledge.

Clinical Trials as Topic↗
PubMed1988

Intravenous infusion of a medium-chain triglyceride-enriched lipid emulsion.

There has been much interest in the parenteral use of medium-chain triglycerides (MCT) as a noncarbohydrate energy source. This study examines the effects of infusion iv into postabsorptive normal subjects with three doses (0.5, 1.0, 1.5 g/kg.15 h) of an emulsion containing 56% MCT and 44% long-chain triglyceride (LCT) and comparing its metabolic effect with infusions of normal saline (NS) and an emulsion containing LCT alone. There were significant increases in serum beta-hydroxybutyrate and acetoacetate 5 and 15 h after the start of the MCT-LCT infusions. Increases were seen only after 15 h of NS, while none was observed during LCT alone. Triglycerides were increased in a dose-related fashion with MCT-LCT and were increased even further with LCT alone. Glycerol increased in a dose-related fashion both during the MCT-LCT and LCT infusion beginning immediately (0.5 h) after the start of the infusion. With NS infusion, glycerol increased significantly only after 15 h of infusion. The MCT-LCT mixture and the highest LCT dose resulted in a significant (12%) increase in oxygen consumption after 5 h of infusion. There was no difference in oral glucose tolerance between the various infusions. Infusion of MCT results in significant ketogenesis and more study is needed to determine its clinical utility.

Acetoacetates↗
PubMed1984

Gastric handling of medium-chain triglycerides and subsequent metabolism in the suckling rat.

We have previously shown that preduodenal lipases account for 50% of the lipolytic capacity of 14-day-old rats. The present investigation was designed to study the kinetics of and optimal conditions for absorption of fat in the stomach of suckling rats and its subsequent distribution in the body. After the simultaneous instillation of medium-chain triglycerides (MCT) containing 1.25 microCi 2,3-[3H]trioctanoate and of long-chain triglycerides containing 1.25 microCi 1-[14C]glycerol trioleate into the stomach ligated at the pylorus, we were able to show that gastric absorption of fat is limited to MCT. Two and a half minutes after injection, 88.6% of the radioactivity in the wall of the stomach was associated with free fatty acids, proving that lipolysis had preceded the absorption of the majority of the MCT. The remainder of the radioactivity was found in mono-, di-, and triglycerides as well as with cholesterol ester and phospholipids. In the plasma, peak radioactivity was attained within 2.5 min and a steady state ensued which lasted at least 30 min. Over this time period, specific radioactivity continued to rise in the liver, suggesting that hepatic uptake proceeded at the same rate as gastric absorption. Uptake could also be demonstrated in the three other organs tested, the lungs, the heart, and the kidneys. Absorption of MCT at pH 3 was only 20% of absorption at pH 6, which is the physiological pH in the suckling rat stomach within the first 10 min after a feed. Both at pH 3 and at pH 6, the addition of sodium taurocholate increased absorption of MCT over threefold. It is likely that the absorption of MCT by the stomach is a physiological event in the suckling rat.

Absorption↗
PubMedDate not supplied

Diurnal and within-feed variations in lipase activity and triglyceride content of human milk.

This study examined the diurnal and within-feed variations in the two lipases of human milk, bile-salt-stimulated lipase (BSSL) and lipoprotein lipase (LPL). In addition, all milks were also analyzed for triglyceride content. As compared to BSSL, LPL activity was more variable both among mothers and among different samples from the same mother (largest variation, 0-2.8 U/ml milk). The only significant variation in lipase activity was in LPL activity during a 24-h period (0.96 +/- 0.113, 0.52 +/- 0.21, and 0.57 +/- 0.092 U/ml milk at 0801-1600, 0001-0800, and 1601-2400 h, respectively) (p less than 0.05). Triglyceride content showed no significant diurnal variation but did increase significantly during a single feeding (31 +/- 9.4, 52 +/- 11.7, and 72 +/- 14.8, mumoles triglyceride/ml milk for fore-, mid-, and hind-milks, respectively) (p less than 0.05). There was no correlation between either LPL or BSSL activity and triglyceride content of the milks. Our data indicate that milk obtained for banking or research purposes will contain similar levels of BSSL activity irrespective of diurnal or within-feed timing of milk collections.

Circadian Rhythm↗
PubMedDate not supplied

The effects of formula change on triglycerides and free fatty acids in preterm infants.

We measured preprandial and 2-h postprandial plasma triglycerides (TG) and free fatty acids (FFA) in 13 preterm infants weekly for 3 consecutive weeks to examine the effects of a premature, medium-chain triglyceride (MCT)-containing formula advancing to a term, long-chain triglyceride (LCT)-containing formula. The infants were on premature formula for the first 2 weeks of the study and were switched to term formula 4-5 days before the last sampling. Significant increases were seen in preprandial and 2-h postprandial TG when the infants were advanced from the premature to the term formula. It was speculated that this increase was due to the predominance of LCT in term formula, which differed in its absorption and metabolism from MCT. Whether these increases persist and if their clinical significance requires further investigation. No consistent change was observed in the preprandial or postprandial FFA.

Fatty Acids, Nonesterified↗
PubMed1992

Medium chain triglyceride in the therapy of gastroesophageal reflux.

Carbohydrate solutions that empty rapidly from the stomach have been shown to produce less gastroesophageal reflux (GER) during the postcibal period than more slowly emptying formulas. These observations have not been extended to complete infant formulas containing fat, carbohydrate, and protein constituents. Medium chain triglyceride has been shown to significantly accelerate gastric emptying compared to long chain triglyceride for preterm infants when investigated in commercial infant formulas. Using a previously reported acidified formula model coupled with esophageal pH probe testing, we have documented in a group of 28 infants that modification of formula by enrichment with medium chain triglyceride produced no improvement in rates of GER during the first 2 h after feeding.

Gastroesophageal Reflux↗
PubMed1998

Lipid digestion in cystic fibrosis: comparison of conventional and high-lipase enzyme therapy using the mixed-triglyceride breath test.

BACKGROUND: Fat maldigestion occurs in most patients with cystic fibrosis. Conventional pancreatic enzyme replacement therapy partially corrects this defect. In this study, the mixed-triglyceride breath test was used to evaluate whether high-lipase enzymes are equivalent to conventional enzymes in improving fat maldigestion in children with cystic fibrosis. METHODS: Fat digestion was studied in 11 patients with a mean age of 10.5 years. The mean intake of conventional enzyme capsules a day was 19. Four 13C mixed-triglyceride tests were performed on separate days and in random order. One test was taken without enzyme substitution, one with three capsules of 8,000 FIP units Creon (pancreatinum, Kali-chemie Pharma, Hannover, Germany) and one with one capsule of 25,000 FIP units. The fourth test was made with 13C octanoic acid to study gastric emptying time. RESULTS: Without enzyme intake, the mean cumulative percentage of 13C dose exhaled after 6 hours was 7.2+/-3.7%. This increased to 14.4+/-4% with intake of conventional pancreatinum and to 14.3+/-5.1% with intake of high-lipase pancreatinum (p = 0.0008 for both; paired t-test). There was no difference between both treatments. Also, the time course of 13C exhalation measured by percentage of 13CO2 exhaled per hour did not differ between enzyme treatments. CONCLUSIONS: The 13C mixed-triglyceride test is noninvasive and documents improved lipid digestion with pancreatic enzyme replacement therapy. If the lipase dose is kept constant, results obtained with high-lipase preparations are equivalent to those obtained with conventional preparations.

Adolescent↗
PubMed1984

Inhibition of hepatic cholesterol and triglyceride synthesis by guanabenz acetate.

Abundant evidence exists for the cumulative adverse effects of hypertension and hypercholesterolemia on the progression of coronary heart disease. The antihypertensive drug guanabenz acetate has been shown to lower serum cholesterol levels, but the mechanism for this effect is unclear. To explore this problem, suspensions of rat liver cells were incubated with guanabenz and labeled lipogenic precursors. Guanabenz produced an inhibition of cholesterol production from [14C]acetate that ranged from 10% at 0.005 mM guanabenz to 90% at 0.20 mM guanabenz. Inhibition of cholesterol production from [14C]mevalonate was half as great as inhibition from [14C]acetate. Thus, guanabenz inhibits hepatic cholesterol production at both pre- and postmevalonic sites in the sterol pathway. Synthesis of triglycerides from [14C]palmitate also was inhibited by guanabenz, whereas oxidation of [14C]palmitate to 14CO2 was stimulated. Therefore, the inhibition of triglyceride formation from fatty acid produced by guanabenz may be due to the stimulation of fatty acid oxidation. The clinical effects of guanabenz on serum lipid levels may relate to its direct actions on hepatic cholesterol and triglyceride biosynthesis.

Animals↗
PubMed1988

Acute and chronic effects of dihydropyridines on triglycerides in humans.

Several drugs used in the treatment of hypertension have been shown to affect lipid metabolism. A few studies have examined in detail the effects of calcium antagonists on blood lipids. We investigated the effects of nifedipine and nitrendipine on blood lipids using two experimental protocols. The first study was a double-blind, randomized, placebo-controlled trial to assess the effects of acute oral administration of nifedipine 10 mg on blood lipids in 10 patients (9 males, 1 female; age range 26-50 years) with mild hypertriglyceridemia. Serum triglycerides were not significantly affected (from 310 +/- 120 to 280 +/- 110 mg/dl 2 h after nifedipine) but a slight decrease was observed in patients with higher baseline levels. In the second study, an intravenous fat tolerance test (ivFTT, Intralipid 10%, 1 ml/kg body weight, as a bolus) was performed before and after chronic oral administration of nitrendipine 10 mg b.i.d. in 10 mild to moderate hypertensive patients (7 males, 3 females; age range 40-60 years). After nitrendipine treatment, the fractional removal rate (K2) of the lipid emulsion was significantly increased from 3.1 +/- 0.9 to 3.8 +/- 0.9% min (p less than 0.05). The main findings of these studies suggest that the secretion of lipoprotein lipase might be stimulated by calcium antagonists. Alternatively, the vasodilation produced by these compounds may influence triglyceride removal by expanding the capillary bed where the enzyme exerts its activity. In conclusion, calcium antagonists do not seem to cause unwanted side effects on blood lipids and apparently enhance triglyceride removal.

Adult↗
PubMed2000

Familiality of triglyceride and LPL response to exercise training: the HERITAGE study.

PURPOSE: The main purpose of the present investigation was to test whether and to what extent familial/genetic factors are involved in the changes of postheparin lipoprotein lipase (deltaPH-LPL) activity and triglyceride (deltaTG) levels in response to exercise training. Additional hypotheses were also tested as to whether there were familial/genetic factors shared by baseline and the corresponding response to exercise training (i.e., by baseline triglyceride (TG(B)) and deltaTG and by baseline postheparin lipoprotein lipase (PH-LPL(B)) and deltaPH-LPL activity). METHODS: Serum TG and PH-LPL were measured in 459 subjects from 99 sedentary Caucasian families of the HERITAGE Family study before (baseline) and after completing a 20 wk (3 times per week) exercise training protocol. The training protocol had a target intensity of 75% of the heart rate associated with baseline VO2max during the last 6 wk. PH-LPL activity was measured in the study subjects. Both univariate and bivariate familial correlation analyses were applied to the baseline and response data. RESULTS: The maximal heritabilities for deltaTG and deltaPH-LPL activity were 22% and 15%, respectively. There were no common familial factors for TG(B) and deltaTG, nor were there any for PH-LPL(B) and deltaPH-LPL. However, we found that there were common familial factors underlying deltaTG and deltaPH-LPL; these familial factors seemed to differ across sex and generation groups. CONCLUSION: Although there were no common familial factors underlying the covariation between the baseline triglyceride and PH-LPL activity and the corresponding responses to exercise training (i.e., TG(B) with deltaTG or PH-LPL(B) with deltaPH-LPL), the deltaTG and deltaPH-LPL covariation apparently share some common familial determinants.

Adolescent↗
PubMed1981

The effects of differential psychological stress and infantile handling on plasma triglyceride and aortic cholesterol levels in rats.

The effects of differential psychological stress on serum triglyceride and aortic cholesterol levels were investigated in two experiments. In the first, rats with an unknown infant handling history purchased as adults from a standard supplier were subjected to predictable, controllable shocks; unpredictable, uncontrollable shocks; or the apparatus or their home cages with no shocks, for 30 days. All were maintained on a cholesterol-supplemented diet except during the daily 51-min stress sessions. The amounts eaten were equated among the groups. The results that the shocked rats had significantly lower terminal levels of serum triglycerides, and those receiving unpredictable, uncontrollable shocks had significantly less aortic cholesterol, than the nonshocked groups, which did not differ from each other in either measure. In the second experiment, rats born in this laboratory were either handled or left undisturbed in infancy and were exposed to a diet and differential stress conditions as adults. Animals handled in infancy had significantly lower aortic cholesterol than nonhandled animals across all stress conditions. In addition, those exposed to unpredictable, uncontrollable shocks had lower aortic cholesterol than those exposed to predictable, controllable shocks, and both had lower aortic cholesterol than the nonshocked group. Similar differential stress effects across stress conditions were seen in all the rats' serum triglyceride levels in Experiment 2. The effects of infantile handling did not interact with the stress effects, and neither could be accounted for by group differences in amount of the diet eaten or weight gained.

Animals↗
PubMed2000

Triglyceride synthesis: insights from the cloning of diacylglycerol acyltransferase.

Although the biochemistry of triglyceride synthesis has been studied for decades, an understanding of the molecular processes involved has been lacking. The recent cloning of a gene encoding acyl coenzyme A : diacylglycerol acyltransferase, an enzyme that catalyses the final step in triglyceride synthesis, has opened this area to molecular investigation and has begun to provide new insights into triglyceride metabolism.

Acyltransferases↗
PubMed2005

A secreted lipase encoded by LIP1 is necessary for efficient use of saturated triglyceride lipids in Fusarium graminearum.

A triglyceride lipase gene LIP1 was identified in the genome of Fusarium graminearum strain PH-1. The predicted protein encoded by LIP1 contains 591 amino acid residues with a putative N-terminal signal peptide and shows 57 and 40-44 % identity to a Botrytis cinerea lipase and five Candida rugosa lipases, respectively. Yeast cells overexpressing LIP1 showed lipolytic activity against a broad range of triglyceride substrates. Northern blot analyses revealed that expression of LIP1 was activated in planta during the fungal infection process. LIP1 expression was strongly induced in minimal medium supplemented with wheatgerm oil, but only weakly induced by olive oil and triolein. In contrast, supplementation with other carbon sources, including glucose, sucrose, apple pectin and wheat cell-wall material, did not induce LIP1 expression. Saturated fatty acids were the strongest inducers for LIP1 expression and this induction was suppressed proportionally by the presence of the unsaturated fatty acid. To determine the potential function of LIP1, gene replacement was conducted on strain PH-1. When compared with wild-type PH-1, DeltaLIP1 mutants showed greatly reduced lipolytic activities at the early stage of incubation on minimal medium supplemented with either saturated or unsaturated lipid as the substrate, indicating that LIP1 encodes a secreted lipase for exogenous lipid hydrolysis. Moreover, the DeltaLIP1 mutants exhibited growth deficiency on both liquid and solid minimal media supplemented with the saturated triglyceride tristearin as the sole carbon source, suggesting that LIP1 is required for utilization of this substance. Despite these differences, no variation in disease symptoms between the DeltaLIP1 mutants and the wild-type strain was observed on susceptible cereal hosts.

Fusarium↗
PubMed2003

Uric acid or 1-methyl uric acid in the urinary bladder increases serum glucose, insulin, true triglyceride, and total cholesterol levels in Wistar rats.

In animals deprived of food for a long period, a drop in the fat mass below 5% of the total body mass results in an increase in blood glucocorticoids and uric acid levels, followed by foraging activity. Since the glucocorticoids increase the uric acid excretion, an increase in the level of uric acid in the bladder urine could be the signal for this feeding behaviour and subsequent fat storage. Accumulation of fat is associated with hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and hypercholesterolaemia as seen in the metabolic syndrome or hibernation. It is hypothesized that uric acid or its structurally related compound, 1-methyl uric acid (one of the metabolites of the methyl xanthines namely caffeine, theophylline, and theobromine present in coffee, tea, cocoa, and some drugs), can act on the urinary bladder mucosa and increases the blood glucose, insulin, triglyceride, and cholesterol levels. In rats, perfusion of the urinary bladder with saturated aqueous solution of uric acid or 1-methyl uric acid results in a significant increase in the serum levels of glucose, insulin, true triglyceride, and total cholesterol in comparison with perfusion of the bladder with distilled water at 20, 40, and 80 min. The uric acid or the 1-methyl uric acid acts on the urinary bladder mucosa and increases the serum glucose, insulin, true triglyceride, and total cholesterol levels.

Administration, Intravesical↗
PubMed1977

The effect of clofibrate on glucose tolerance, insulin secretion, triglycerides and fibrinogen in patients with coronary heart disease.

The effects of clofibrate treatment have been monitored in a double-blind cross-over study conducted in 16 male patients with coronary heart disease. Most had latent diabetes mellitus with elevated and delayed insulin release after i.v. glucose administration. Blood glucose and insulin levels were measured during repeated i.v. glucose tolerance tests in each patient and serum triglyceride and plasma fibrinogen were estimated at intervals. Clofibrate treatment significantly lowered fasting blood glucose levels (p less than 0.01) and improved the glucose tolerance (p less than 0.01). Fasting plasma insulin levels and those at 30 min after glucose loading were reduced (p less than 0.05). Serum triglycerides (p less than 0.01) and plasma fibrinogen levels (p less than 0.05) were lowered during the treatment period. The change in k-value (glucose utilization) did not correlate to changes in triglyceride or fibrinogen. This study confirms the beneficial effect of clofibrate therapy on abnormal glucose tolerance observed by other workers. It is suggested that clofibrate acts by reducing peripheral insulin resistance.

Adult↗
PubMed1983

Fasting serum cholesterol and triglycerides in a ten-year prospective study in old age.

In a ten-year prospective study of a population of men and women aged exactly 70 at entry and otherwise selected only according to geography, the predictive values of serum cholesterol and serum triglycerides were evaluated concerning total mortality and cardiovascular disease (CVD) and cancer manifestations in the eighth decade. Both high and low cholesterol values at 70 were associated with excess total mortality in men, the former showing excess CVD mortality, the latter excess cancer mortality. In men, high values of triglycerides at 70 were associated with increased CVD mortality as well as CVD development. In women, high values of triglycerides at 70 were associated with excess hospitalization for cerebrovascular incidence alone.

Aged↗
PubMed1985

Triglycerides--main lipid risk factor for cardiovascular disease in women?

A 12-year longitudinal population study of 1462 women, aged 38-60, was carried out in Gothenburg, Sweden in 1968-69. Women with high initial serum triglyceride values had a higher 12-year incidence of myocardial infarction, stroke and total mortality than the others. The findings for serum triglycerides persisted for myocardial infarction, stroke and total mortality after adjustment for other possible risk factors for ischaemic heart disease such as age, systolic blood pressure, smoking, indices of obesity and serum cholesterol, while serum cholesterol did not predict any end-points studied when taking other risk factors including serum triglycerides into account.

Adult↗
PubMed1982

Metabolic disorders of serum lipoproteins in endotoxin-poisoned mice: the role of high density lipoprotein (HDL) and triglyceride-rich lipoproteins.

A study was performed to clarify the role of serum lipoproteins, especially high density lipoprotein (HDL) and triglyceride-rich lipoproteins in endotoxemic or endotoxin-poisoned animals. The level of HDL-cholesterol decreased markedly in mouse serum 18-24 hr postintoxication, while the amount of low density lipoprotein (LDL)-cholesterol in the sera of poisoned mice was about 175% of that of the controls. Serum lecithin-cholesterol acyltransferase activity in the poisoned mice decreased slightly for 3-6 hr after endotoxin injection, but became markedly increased at 18-24 hr as compared with that in the controls. The amount of serum very low density lipoprotein (VLDL) showed a marked increase in the poisoned mice 8-24 hr postintoxication. The HDL fraction in the electrophoretic patterns of serum was reduced according to the dose of endotoxin 18 hr postintoxication. The HDL fraction in mice injected with lead acetate plus endotoxin was markedly lower than that in the poisoned mice. When streptozotocin-diabetic mice were injected with endotoxin, the HDL fraction was higher than that in the endotoxin-poisoned mice. In endotoxin-poisoned mice a correlation was observed between the lipid peroxide and LDL levels in the serum. In disk electrophoretic patterns, the HDL fraction in mice given vitamin E-supplemented diet showed a higher level than that in mice given a normal diet. Lipoprotein lipase (LPL) activity in poisoned mice significantly decreased to 59% of the control value 18 hr postintoxication, but hepatic triglyceride lipase activity was only slightly increased in endotoxin-poisoned mice. In analysis of HDL apoprotein peptide in serum lipoprotein, the apo C-II peptide level was clearly lower in mouse serum 18 hr postintoxication than that in the controls. These results suggest that the decrease in LPL activity in endotoxin-poisoned mice may be closely related to a decrease in the apo C-II peptide level, and also that it plays an important part in HDL and triglyceride-rich lipoprotein metabolism in the poisoned mice.

Animals↗