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PubMed2000

Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight.

Activators of peroxisome proliferator activated receptors (PPARs) are effective drugs to improve the metabolic abnormalities linking hypertriglyceridemia to diabetes, hyperglycemia, insulin-resistance, and atherosclerosis. We compared the pharmacological profile of a PPARalpha activator, fenofibrate, and a PPARgamma activator, rosiglitazone, on serum parameters, target gene expression, and body weight gain in (fa/fa) fatty Zucker rats and db/db mice as well as their association in db/db mice. Fenofibrate faithfully modified the expression of PPARalpha responsive genes. Rosiglitazone increased adipose tissue aP2 mRNA in both models while increasing liver acyl CoA oxidase mRNA in db/db mice but not in fatty Zucker rats. Both drugs lowered serum triglycerides yet rosiglitazone markedly increased body weight gain while fenofibrate decreased body weight gain in fatty Zucker rats. KRP 297, which has been reported to be a PPARalpha and gamma co-activator, also affected serum triglycerides and insulin in fatty Zucker rats although no change in body weight gain was noted. These results serve to clearly differentiate the metabolic finality of two distinct classes of drugs, as well as their corresponding nuclear receptors, having similar effects on serum triglycerides.

Acyl-CoA Oxidase↗
PubMed1978

Affinity chromatography on heparin-sepharose of rat adipose tissue triglyceride lipase from cytosol.

Subfractionation of the fat free homogenate of rat adipose tissue showed that a high yield of triglyceride lipase was recovered reproducibly in the microsomal supernatant fraction (cytosol) when rat epididymal fat pads were homogenized in sucrose-EDTA-Tris medium. Triglyceride lipase was bound on heparin-Sepharose. Hydrolyzing activity towards triacylglycerol was eluted as a single, sharp peak in 0.7 M NaCl, 5 mM sodium barbital and 20% glycerol (pH 7.0). The triglyceride lipase was not inhibited by 1 M NaCl and not stimulated by the presence of fresh human serum. A lipoprotein-lipase activity was demonstrable in the cytosol when adipose tissue from fed rats were used. Fasting of the animals lowered this activity.

Adipose Tissue↗
PubMed1993

Relationship between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, insulin levels and insulin sensitivity: studies in randomly selected normo- and hypertriglyceridaemic men.

Impaired fibrinolytic function secondary to elevated plasma plasminogen activator inhibitor-1 activity, hypertriglyceridaemia and hyperinsulinaemia are frequent findings in patients with coronary heart disease. It has been debated whether VLDL or insulin is the major regulator of plasma plasminogen activator inhibitor-1 activity. This study examines the relationships between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, fasting and post-oral glucose load insulin levels and insulin sensitivity, as estimated by the minimal model method. Subjects studied were randomly selected hypertriglyceridaemic (n = 65) and age-matched normotriglyceridaemic (n = 61) men, aged 40-50 years, recruited in a population survey. Plasma plasminogen activator inhibitor-1 activity was higher in the hypertriglyceridaemic than in the normotriglyceridaemic group (21 +/- 14 vs 10 +/- 8 mU/l; p < 0.01). The hypertriglyceridaemic group had higher serum insulin, basal as well as 2 h after intake of the oral glucose load, and a lower insulin sensitivity index. In univariate analysis, plasma plasminogen activator inhibitor-1 activity correlated positively with VLDL triglycerides in both the hyper- and normotriglyceridaemic groups (r = 0.43 r = 0.60, respectively) and negatively with the insulin sensitivity index (r = -0.35 r = -0.44, respectively). In multivariate analysis, VLDL triglyceride levels were found to be independently related to plasma plasminogen activator inhibitor-1 activity in both groups, whereas insulin sensitivity/serum insulin levels were not. An unexpected finding was that the serum activity of the enzyme gamma glutamyl transpeptidase appeared to influence the relationships for plasma plasminogen activator inhibitor-1 in the hypertriglyceridaemic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Postprandial triglyceride response in type 1 (insulin-dependent) diabetes mellitus is not altered by short-term deterioration in glycaemic control or level of postprandial insulin replacement.

UNLABELLED: The effect of deteriorating glycaemic control on the lipoprotein responses to the ingestion of a high fat meal was investigated in seven normolipidaemic Type 1 (insulin-dependent) diabetic patients and the results were compared with corresponding responses in seven normolipidaemic control subjects. In addition, the importance of insulin in regulating the postprandial lipoprotein responses was examined by comparing the results obtained from the diabetic patients maintained on a basal infusion of insulin throughout the study with those obtained when a step-up, step-down insulin infusion was administered following the meal. Vitamin A was added to the test meal in all subjects to trace the metabolism of the chylomicron (Sf greater than 1000) and non-chylomicron (Sf less than 1000) fractions in the postprandial period. No differences in fasting and postprandial triglyceride levels nor in the concentration of the chylomicron and non-chylomicron fractions were observed between diabetic and control subjects. In the diabetic patients short-term (two-week) deterioration in glycaemic control did not have any adverse influence on the basal and postprandial lipid responses. However, while the amount of insulin administered after the meal in the diabetic patients did not have any effect on the postprandial triglyceride or chylomicron responses, the concentration of non-esterified fatty acids was significantly higher (p less than 0.0005) when only a basal infusion of insulin was administered. IN CONCLUSION: 1) Short-term deterioration in glycaemic control does not adversely affect lipoprotein concentrations in Type 1 diabetes. 2) Non-esterified fatty acids appear to be a more sensitive index of insulinization post-prandially than triglycerides.

Adult↗
PubMed1990

Association of plasma triglyceride and C-peptide with coronary heart disease in Japanese-American men with a high prevalence of glucose intolerance.

In a community-based study of second-generation Japanese-American men known to have a high prevalence of both Type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance, there was a highly significant association of coronary heart disease with glucose intolerance in a study sample of 219 men. Intra-abdominal cross sectional fat area determined by computed tomography was significantly elevated in men with coronary heart disease even after adjustment for glucose intolerance and body mass index (p = 0.026). Other differences that were significantly related to coronary heart disease after adjustment for glucose intolerance were lower high density lipoprotein cholesterol levels (p = 0.001), elevated total triglyceride and very low density lipoprotein triglyceride (p less than 0.001), and elevated fasting insulin and C-peptide levels p = 0.001. When these variables were tested in a stepwise multiple logistic regression model, significant independent associations with coronary heart disease were found only for total triglyceride and fasting C-peptide after adjustment for glucose tolerance status. Variables identified to be associated with coronary heart disease were interpreted as representing or manifesting an insulin resistant state. Thus, insulin resistance may be the underlying risk factor aetiologically linking glucose intolerance with coronary heart disease.

Alcohol Drinking↗
PubMed1989

Effect of exposure to cold and fasting on the placental glycogen and triglyceride content in the rat.

The effect of exposure to cold (+2 degrees C, 3 and 24 h) and fasting (1, 2 and 3 days) on placental glycogen and triglyceride content was investigated in rats pregnant for 20 days. The stimuli did not affect the level of glycogen in the placenta. The level of triglycerides remained unchanged in the rats exposed to cold. It rose after only one day of fasting and then levelled out on the 2nd and 3rd days. Fasting, but not exposure to cold produced hypoglycemia and elevation of the plasma free fatty acids level. We conclude that activation of the adrenergic system during exposure to cold does not interfere with the glycogen and triglyceride content of the placenta. Prolonged hypoglycemia also does not affect the placental glycogen level although it increases the accumulation of neutral fat.

Animals↗
PubMed1987

Comparison of effects of ingested medium- and long-chain triglyceride on gallbladder volume and release of cholecystokinin and other gut peptides.

In a double-blind, crossover study of the effect of ingested medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) in six normal subjects, the gallbladder did not contract after ingestion of MCT but instead had significantly increased in volume at 2 hr after the meal. Plasma cholecystokinin (CCK) increased after the MCT meal, but gastrin, motilin, pancreatic polypeptide (PP), and GIP were unaffected. The long-chain triglyceride meal evoked a brisk and sustained gallbladder contraction, higher levels of CCK, and a significant increase in plasma PP and GIP levels.

Adult↗
PubMed1993

Parenteral nutrition in the critically ill: use of a medium chain triglyceride emulsion.

OBJECTIVES: The study investigated the use of an intravenous lipid emulsion containing medium chain triglycerides (MCTs) in critically ill patients, and compared the effects with those of a conventional long chain triglyceride (LCT) preparation. DESIGN: Patients received a parenteral nutrition regime including either 500 ml 20% Lipofundin MCT/LCT (1/1) per day, or 500 ml 20% Lipofundin S (LCT) infused over 8 h each evening. SETTING: The patients were receiving treatment, including assisted ventilation, in the Intensive Care Unit of a large teaching hospital. All patients on this unit for at least 3 days and who were likely to receive parenteral nutrition for at least a week were considered, unless they had severe renal or liver disease, or trauma/major surgery in the previous 3 days. Because ICU patients are a heterogenous group, subjects were randomised within clinical groups to receive either lipid. There were 24 patients entered into the study and the data on 20 matched patients is reported. MEASUREMENTS AND RESULTS: Blood specimens were collected pre-TPN, daily at 0800 and after 5 h lipid infusion on days 1 and 6. Urine collections (24 h) were also performed. There were no apparent adverse effects due to the new MCT/LCT emulsion. Plasma ketone and glycerol concentrations were higher during MCT/LCT infusion, but 8 h post infusion plasma levels of ketones, triglycerides, non-esterified fatty acids and glucose were similar. Urinary carnitine excretion was high in all patients and was not significantly different between the groups. Nitrogen balance was less negative in patients receiving MCT/LCT on days 6 and 9. CONCLUSION: MCTs are rapidly hydrolysed and oxidised to fatty acids and ketones which can be readily utilised. This study indicates that intravenous lipid emulsion containing MCT are safe in critically ill patients and may have advantages over LCT. The number and range of patients studied was, however, small and larger studies are needed.

3-Hydroxybutyric Acid↗
PubMed1993

High PAI activity with correlation to triglyceride and HDL cholesterol values in patients with coronary artery disease with no difference in survivors of myocardial infarction.

The fibrinolytic capacity of blood depends mainly on the amount of tissue-type plasminogen activator (t-PA) activity and plasminogen activator inhibitor type-1 (PAI-1) activity. Previous studies linked high PAI activity or low t-PA activity with the development of atherosclerosis and thromboembolic diseases. Yet, there are conflicting reports in the literature as to whether there is higher PAI activity in patients with myocardial infarction (MI) than in patients with coronary artery disease (CAD) without previous MI. In this retrospective study, t-PA activity, t-PA antigen, and PAI activity before and after a venous occlusion test (VOT) of 10 min were assessed in 109 patients with angiographically documented CAD, in two subgroups of CAD patients with (n = 66) or without (n = 43) previous MI, and in subgroups of CAD patients according to their triglyceride levels and other risk factors. The mean values of t-PA activity in the whole patient group showed a 100-fold increase and a 3.1-fold increase in t-PA antigen after VOT (0.03 +/- 0.03 to 3.0 +/- 6.8 U/ml and 16.5 +/- 6.9 to 51.0 +/- 25.4 ng/ml, p < 0.05). PAI activity was 24.4 +/- 11.0 before and 19.6 +/- 13.2 U/ml after VOT. Within the CAD group, no difference was found between patients without MI and survivors of previous MI in PAI activity before VOT (24.6 +/- 10.7 vs. 24.3 +/- 11.3 U/ml) and after VOT (19.0 +/- 12.1 vs 20.0 +/- 14.0 U/ml), or t-PA activity before (0.03 +/- 0.01 vs. 0.04 +/- 0.04 U/ml) and after VOT (2.8 +/- 7.0 vs. 3.2 +/- 6.7 U/ml). In 39.4% of CAD patients elevated plasma PAI activity before VOT (> 25 U/ml) was found. This subgroup of patients represented the highest PAI activity after VOT (p < 0.05), the lowest t-PA activity after VOT (p < 0.001), and the highest triglyceride levels (p < 0.05). In 11% of the patients, a small increase in t-PA activity (less than 0.5 U/ml) after VOT was seen. This group showed the lowest t-PA antigen after VOT (p < 0.001) and the highest fibrinogen level (p < 0.05). Both subgroups showed the same distribution among patients with and without MI. CAD patients with triglyceride levels over 200 mg/dl had the highest PAI activity values before VOT (28.3 +/- 11.8 U/ml; p < 0.01) and after VOT (24.9 +/- 13.2 U/ml; p < 0.01), resulting in low t-PA activity after VOT (p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Cholesterol, HDL↗
PubMed1979

Sex-dependence in triglyceride metabolism in response to dietary carbohydrates.

In humans, as well as in mice, fed on high carbohydrate diets, there was a significant sex difference in the plasma tirglycerides in that males had higher levels than females. This was mainly due to the difference in their removal rate of circulating triglycerides in the animals of both sexes. In mice, males had higher levels of liver triglycerides as well as higher rate of incorporation of U- 14C-glucose into liver triglycerides when compared to females.

Adult↗
PubMed1985

Effect of fasting on skeletal muscle triglyceride content.

The effect of prolonged food deprivation on the triglyceride level in different types of skeletal muscle was studied in the rat. It has been found that fasting gradually reduces the triglyceride content in each muscle type. It is concluded that i.m. triglycerides play an important role as energy fuel during fasting.

Animals↗
PubMed1996

Elevated triglyceride-rich lipoproteins in diabetes. A study of apolipoprotein B-48.

The role of the intestine in cholesterol metabolism in human diabetes is unclear, although abnormalities have been demonstrated in cholesterol synthesis and absorption in diabetic animals. This study examines the relationship between fasting and post-prandial apolipoprotein B-48 in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Eight type 2 diabetic patients and ten healthy non-diabetic control subjects were given a high-fat meal (1300 kcal), and the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (d < 1.006 g/ml) from fasting and post-prandial plasma. Apolipoprotein B-48 and apo B-100 were separated on 4%-15% gradient gels and quantified by densitometric scanning with reference to a purified low-density lipoprotein (LDL) apo B-100 preparation. Diabetic patients had significantly higher concentrations of apo B-48 and apo B-100 in both the fasting (P < 0.05) and post-prandial (P < 0.001) triglyceride-rich lipoprotein samples compared with non-diabetic subjects. The diabetic patients also exhibited a significantly different post-prandial profile for apo B-48 and apo B-100, with a prolonged increase and a later post-prandial peak, than the non-diabetic subjects (P < 0.01). These results suggest that the raised fasting triglyceride-rich lipoproteins, often found in diabetes, are associated with apo B-48 and may be derived from increased intestinal chylomicron production. The post-prandial pattern suggests an abnormality in intestinal production as well as hepatic clearance of apo B-48 in type 2 diabetes.

Apolipoprotein B-100↗
PubMed1981

Differential diagnosis of maldigestion and malabsorption of fat. I. Comparison of the radioactivity of triglyceride and non-esterified fatty acid in fecal fat using purified 131I-triolein.

To differentiate maldigestion from malabsorption of fat, we compared the radioactivity of triglyceride with non-esterified fatty acid in fecal fat after ingestion of radiochemically purified 131I-triolein. A large amount of radioactivity was present in the triglyceride fraction from patients with pancreatic insufficiency, while such was found only in non-esterified fatty acid fraction in patients with short bowel syndrome, as determined by thin-layer chromatogram scanning. Thus, the "Digestion-Absorption Index" was calculated as a ratio of the radioactivity of triglyceride to that of non-esterified fatty acid. Mean Digestion-Absorption Index was 0.946 in the maldigestive group, and 0.045 in the malabsorptive group, and there was a statistical significance. However, an overlap in a few cases was confirmed in the area of 0.10 +/- 0.02, when this index was plotted on a table of semilogarithms. We assumed that this overlap was chiefly the result of maldigestion plus malasorption of fat.

Adult↗
PubMed1978

Distinctive medium chain wax esters, triglycerides, and diacyl glyceryl ethers in the head fats of the Pacific beaked whale, Berardius bairdi.

Lipids were extracted from the mandibular fat body (jaw), the fatty forehead (melon), and the dorsal blubber of a Pacific beaked whale (Berardius bairdi) and separated into lipid classes by preparative thin layer chromatogrphy. The head fats were mixtures of wax esters and triglycerides with a very small amount of diacyl glyceryl ether. The blubber fat contained 97% wax ester and 3% triglyceride. Gas liquid chromatography (GLC) of the intac lipid classes indicated an unusually low C26-C30 range for most of the jaw and melon wax esters compared to the more normal C32-C40 molecules found in the blubber. Distinctive lower molecular weight C24-C40 triglycerides occurred in the head fats vs. the usual C44-C58 range in the blubber. Most diacyl glyceryl ethers were in the C35-C46 range, below the molecular weight of hexadecyldipalmitoyl glyceryl ether (C48). GLC of the derived fatty acid methyl esters showed that the lower molecular weight neutral lipids in the head fats were due to high levels of iso-10:0, n-10:0, iso-11:0, iso-12:0, N-12:0, and iso-13:0 acids. The wax ester fatty alcohols and the alkoxy chains of the glyceryl ethers were mostly the C14-C20 chain lengths commonly observed in marine organisms. The distinctive medium chain neutral lipids in the jaw and melon fats of this whale may be related to the postulated acoustical role of these tissues in echolocation.

Adipose Tissue↗
PubMed1975

Positional analysis of isovaleroyl triglycerides using proton magnetic resonance with Eu (fod) 3 and Pr (fod) 3 shift reagents: I. Model compounds.

The proton magnetic resonance spectra of isomeric triglycerides of isovaleric and palmitic acids in the presence of the downfield and upfield chemical shift reagents Eu(fod)(3) and Pr(fod)(3) were studied. The resonance profiles of the gamma-protons on the isovaleroyl chains are distinctive for each of the four possible triglyceride isomers at low shift reagent/triglyceride ratios. With either reagent, the well defined gamma-methyl isovalerate doublets can be used to identify 2-isovaleroyl and 1,3-isovaleroyl structures and to analyze isomeric mixtures. This technique will be useful for positional analysis of natural cetacean triglycerides containing isovaleric acid.

Animals↗
PubMed1983

Stereospecific analysis of triglycerides of Glycine max, Glycine soya, Avena sativa and Avena sterilis strains.

A rapid method for the stereospecific analysis of triglycerides based on enzymatic hydrolysis on thin layer plates was applied to a number of Glycine max, Glycine soya, Avena sativa and Avena sterilis strains. The percentage of each fatty acid on the sn-1-, sn-2- and sn-3-positions was linearly related to the total percentage of the fatty acid in the triglyceride. Large deviations from the common triglyceride pattern were not found.

Dietary Fats↗
PubMed1995

Evidence that dietary arachidonic acid increases circulating triglycerides.

Male Syrian hamsters and male CD-1 mice were fed diets supplemented with ethyl esters of oleic, linoleic, arachidonic, and eicosapentaenoic acids (1.1-5%, w/w) for 3-4 wk. Plasma and serum triglycerides were significantly higher in the arachidonic acid-supplemented animals compared to those in the other supplementation groups. Changes in serum insulin and glucose levels did not appear to be related to the changes in circulating triglycerides observed in the arachidonic acid-supplemented group. These data indicate that dietary arachidonic acid elevates circulating triglyceride levels compared to other unsaturated fatty acids in hamsters and mice by unknown mechanisms.

Animals↗
PubMed2005

Association of a polymorphism in the gene encoding phosphoenolpyruvate carboxykinase 1 with high-density lipoprotein and triglyceride levels.

AIMS/HYPOTHESIS: Phosphoenolpyruvate carboxykinase (PCK) is the key enzyme involved in the regulation of gluconeogenesis. The aim of this study was to identify genetic polymorphisms in potential candidate genes for type 2 diabetes by sequencing all exons in the PCK genes (PCK1 and PCK2), and examining the association with type 2 diabetes and diabetic phenotypes in a Korean population (775 type 2 diabetic patients and 316 normal control subjects). MATERIALS AND METHODS: Twenty-two polymorphisms in PCK1 and PCK2 were identified in a Korean population (n=24) by direct DNA sequencing. The TaqMan genotyping method was applied for genotyping the remainder of the study population. Associations of PCK polymorphisms with the risk of type 2 diabetes and diabetic phenotypes were analysed using logistic and multiple regressions, adjusting for age, sex and BMI. RESULTS: Although no significant associations between the genetic polymorphisms in PCK genes and the risk of type 2 diabetes were detected, in further haplotype analysis, one of the common haplotypes, PCK1 ht3, revealed susceptibility to type 2 diabetes (p=0.006). One 3' untranslated region (UTR) single nucleotide polymorphism (SNP) also showed an association with HDL levels among non-diabetic control subjects: individuals homozygous for the major allele (T/T) had the lowest HDL level (1.11+/-0.32 mmol/l), heterozygotes (T/C) had an intermediate level (1.27+/-0.37 mmol/l), and those homozygous for the minor allele (C/C) had the highest level (1.39+/-0.28 mmol/l) (p=0.000003). This 3' UTR SNP was also associated with triglyceride levels, with a lower triglyceride level observed among individuals who were homozygous for the minor allele (C/C) than among those who were not. CONCLUSIONS/INTERPRETATION: The strong genetic association of HDL and triglyceride levels with variation/haplotype information identified in this study would be useful for further genetic epidemiological studies of this important gene.

5' Flanking Region↗