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The effect of betaine treatment on triglyceride levels and oxidative stress in the liver of ethanol-treated guinea pigs.

We investigated the effect of betaine supplementation on ethanol induced steatosis and alterations in prooxidant and antioxidant status in the liver of guinea pigs. Animals were fed with normal chow or betaine containing chow (2% w/w) for 30 days. Ethanol (3 g/kg, i.p.) was given for the last 10 days. We found that ethanol treatment caused significant increases in plasma transaminase activities, hepatic triglyceride and lipid peroxide levels. Significant decreases in glutathione (GSH), alpha-tocopherol and total ascorbic acid (AA) levels were also observed, but hepatic superoxide dismutase, glutathione peroxidase and glutathione transferase activities remained unchanged as compared with those in controls. Betaine treatment together with ethanol in guinea pigs is found to decrease hepatic triglyceride, lipid peroxide levels and serum transaminase activities and to increase GSH levels. No changes in alpha-tocopherol and total AA levels and antioxidant enzyme activities were observed with betaine treatment in alcohol treated guinea pigs. In addition, histopathological assessment of guinea pigs showed that betaine reduced the alcoholic fat accumulation in the liver. Based on these data, betaine treatment has a restoring effect on the alterations in triglyceride, lipid peroxide and GSH levels following ethanol ingestion.

Alanine Transaminase↗

Effects of moderate increases in dietary polyunsaturated: saturated fat on plasma triglyceride and cholesterol levels in man.

1. The effects of two isoenergetic diets differing only in the values for polyunsaturated: saturated fat (P:S values of 0.2 v. 2.0) were studied in twenty adult human volunteers. 2. A period of 14 d on the high P:S diet failed to produce significant changes in fasting triglyceride levels, though there were individual variations. On the other hand, fasting cholesterol levels dropped by 10% (P less than 0.005). High-density-lipoprotein-cholesterol concentrations were not influenced by changes in the P:S value. 3. Investigations into the mechanism by which changes in the P:S value might affect plasma triglyceride values revealed no consistent effects on very-low-density-lipoprotein kinetics, insulin secretion, insulin sensitivity or free fatty acid concentrations. 4. The results of this study suggest that the largest increase in dietary P:S values that is likely to be obtained on a long-term basis may have only a small effect on plasma triglyceride and cholesterol concentrations.

Adult↗

Improvement of dietary protein utilisation in chicks by medium chain triglyceride.

1. To improve the influence of variation of ME intake, an experiment was carried out using equalized feeding to investigate the comparative effects on protein and energy utilisation in chicks of diets containing medium chain triglyceride (MCT) and long chain triglyceride (LCT). Experimental diets were given at 3 different food intakes, namely, 100, 120 or 147 g/bird/10 d. The diets contained MCT or LCT on an isoenergetic basis. Maize oil and caprylic acid triglyceride respectively, were used as LCT and MCT sources. 2. Body weight gain and food efficiency of chicks significantly increased with the supplement of dietary MCT compared with dietary LCT at all food intakes. Protein retention and the efficiency of protein utilisation (protein retained/protein intake) at all food intakes also significantly increased with dietary MCT, while body fat and fat retention were significantly reduced. Chicks fed the LCT-supplemented diet, on the other hand, had a lower protein retention, but significantly higher fat retention. The value for energy retention and the efficiency of energy utilisation (energy retained/ME intake) were not significantly different between MCT- and LCT-supplemented diets. 3. It was concluded that supplementing MCT to the chick diet would improve body weight gain and protein utilisation while regulating fat deposition compared to the LCT supplemented diet, under equalized feeding conditions.

Adipose Tissue↗

Accumulation of triglycerides in the proximal tubule of the kidney in diabetic coma.

AIMS: The present study was initiated by a very recent histochemical observation of lipid accumulation in the renal cortex of a woman who died in a diabetic coma. Two older reports of lipid accumulation in the kidneys of patients who died, most likely in a state of non-regulated diabetes, supported this observation. We have examined whether lipid accumulation in the renal cortex is characteristic of diabetic coma and, if so, which type of lipid accumulates. METHODS: Three groups were studied. Ten subjects who died in a diabetic coma, eight diabetics who died of known causes unrelated to diabetes, and seven normal control subjects without any diagnosed diabetes who died of known causes. All were subjected to histological examination for lipid accumulation in the renal cortex. Detailed analysis of cortex lipids was performed for two of the subjects who died in a diabetic coma and all diabetic controls as well as non-diabetic control subjects. RESULTS: All subjects who died in a diabetic coma showed vacuolar lesions staining strongly for lipid in the proximal tubules. Neither normal controls nor non-coma diabetics showed these lesions. Compared with normal controls, renal cortex lipid was about tripled in the two analysed diabetic coma subjects due to 60-100-fold increases of triglycerides. The non-coma diabetics did not differ from the other controls with respect to triglycerides or other types of lipid, except that cholesteryl esters were elevated, though still a quantitatively minor component. CONCLUSION: Our findings strongly indicate that vacuolar lesions in the proximal tubules are characteristic of diabetic coma and that they are caused by accumulated triglycerides. Therefore, histological examination of renal cortex using a lipid stain may be a useful forensic tool in establishing diabetic coma as the cause of death.

Adult↗

Associations between breast cancer, plasma triglycerides, and cholesterol.

A case-control study investigating the association between plasma lipids and breast cancer was conducted among women aged 30-80 in Buffalo, NY. All eligible women from a large breast clinic and two area physicians' offices were requested to participate over a one-year period. Subjects completed a health questionnaire and donated a fasting blood sample prior to diagnostic breast biopsies. The 83 women found to have breast cancer (cases) had significantly higher plasma triglyceride values than did the 113 women found not to have breast cancer (controls). Lower plasma beta-carotene values were associated with breast cancer, but only in those women with elevated triglyceride or cholesterol. Plasma cholesterol values were lower in those breast cancer cases presenting with more advanced stages of cancer, suggesting that metabolic effects of clinical and preclinical breast cancer may lower cholesterol levels. Although the limitations of case-control studies are well-recognized, these data suggest an etiologic role for plasma triglycerides and beta-carotene or for related dietary factors.

Adult↗

Elevated levels of plasma triglycerides are associated with histologically defined premenopausal breast cancer risk.

Lipids and lipoproteins have been associated with breast cancer risk; however, published results have been inconsistent. To clarify these associations, we measured fasting lipids in women undergoing breast biopsies. A case-control study examined the association of fasting levels of lipids with histologically defined breast cancer risk. Four groups of premenopausal women were assembled on the basis of histological appearance of breast tissue: 1) no epithelial proliferation (n = 102), 2) proliferation without atypia (n = 53), 3) atypical hyperplasia or carcinoma in situ (n = 53), and 4) node-negative invasive cancer (n = 102). A postoperative fasting blood specimen was analyzed for cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Demographics, risk factors, diet, physical activity, fasting weight, and skin-fold thickness were measured. Triglyceride levels were significantly higher in women with node-negative invasive cancer (0.94 +/- 1.04 mg/ml) than in those with no epithelial proliferation (0.83 +/- 1.04 mg/ml, p = 0.03). This association persisted after adjustment for age, body size, lipids, reproductive and familial risk factors, and previous benign breast problems (p < 0.01), in keeping with an independent association of elevated triglycerides with breast cancer risk.

Adult↗

Increase in total serum triglyceride and phospholipid in kwashiorkor.

Fasting serum lipids in children presenting with protein-energy malnutrition were studied in comparison with those of sex- and age-matched well nourished controls. There was no difference in serum total cholesterol between malnourished and well nourished children. However, serum triglyceride and phospholipid concentrations were significantly higher in children with kwashiorkor or marasmic kwashiorkor than in well nourished controls. It appears that serum concentrations of triglycerides and phospholipids increase with increasing severity of malnutrition, and that fasting serum triglyceride and phospholipid concentrations above 3 mmol/l are jointly predictive of a poor prognosis in malnourished children.

Case-Control Studies↗

Dietary substitution of medium chain triglycerides in subjects with non-insulin-dependent diabetes mellitus in an ambulatory setting: impact on glycemic control and insulin-mediated glucose metabolism.

OBJECTIVE: We have previously shown in an acute inpatient setting that dietary substitution of 77.5% of fat kcal as medium chain triglycerides (MCT) increased insulin-mediated glucose metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM), and that this effect appeared to be mediated by increases in insulin-mediated glucose disposal. The purpose of this study was to test the application of dietary substitution of medium chain triglycerides as an adjunctive tool in ambulatory therapy of NIDDM. METHODS: Five subjects with NIDDM underwent a baseline 6 hour insulin/glucose euglycemic clamp study, with simultaneous 3H-glucose infusion for calculation of glucose disposal rate and hepatic glucose output. Subjects were then randomized to begin one of two 30-day experimental diets, with long chain (LCT) or medium chain triglycerides (MCT), and subsequent crossover to the other diet. A 6 hour euglycemic clamp was repeated after each diet phase. RESULTS: Diet records and urinary organic acid excretion indicated a high level of dietary compliance by the study participants. Postprandial blood glucose excursions were less after one month on the diet with MCT than after the LCT diet (p = 0.004). However, fasting serum glucose, serum fructosamine (a measure of glycemia), fasting insulin, hepatic glucose output, and insulin-mediated glucose metabolism were not improved by the dietary substitution of MCT. CONCLUSION: These data indicate that supplementation of a tolerable amount of MCT in a conventional diabetic exchange diet has little impact on glycemic control in subjects with NIDDM in an ambulatory setting.

Adult↗

Dysprosium chloride as a nonabsorbable gastrointestinal marker for studies of stable isotope-labeled triglyceride excretion in man.

OBJECTIVE: The aim of this work was to determine if dysprosium chloride (DyCl(3)) is a suitable nonabsorbable marker for studies of labeled-triglyceride excretion in cystic fibrosis patients allowing excretion to be determined accurately after analysis of one or two stools. METHODS: A series of 66 absorption studies were conducted in 36 young cystic fibrosis patients over a five year period. All tests consisted of ingesting a single test meal containing both (13)C-labeled triglyceride (TG*) and DyCl(3); in most studies the food colorant brilliant blue (FD&C blue #1) was administered along with the DyCl(3). Ingestion of the test meal was followed by collection of individual stools for 72 to 96 hours. Stools were analyzed for (13)C-Excess ((13)C*) and Dy. RESULTS: Excretion of Dy in cystic fibrosis patients who exhibited a wide-range of steatorrhea was quantitative. Fractional excretion of Dy and (13)C* in individual stools showed a high linear correlation (r(2) = 0.969) with a slope and y-intercept close to unity and zero, respectively. As a result, estimates of TG* excretion based on analysis of only two stools (partial pool method, PPM) were not different from those based on the analysis of all stools or stool composites. This was true both when Dy content and when stool color due to ingested brilliant blue was used to determine which stools to analyze for the PPM. CONCLUSIONS: Combining the use of Dy and brilliant blue permits reasonably accurate estimates of fecal TG* excretion after analysis of samples from two easily identified stools. This practical method can be used to address many important clinical and experimental questions regarding triglyceride digestion and absorption that may otherwise go unanswered.

Absorption↗

Contribution of apo CIII reduction to the greater effect of 12-week micronized fenofibrate than atorvastatin therapy on triglyceride levels and LDL size in dyslipidemic patients.

BACKGROUND: Apolipoprotein (apo) CIII plays an important role in the catabolism of triglyceride-rich lipoproteins as it is a potent inhibitor of lipoprotein lipase (LPL). A low LPL activity has been simultaneously associated with hypertriglyceridemia, low HDL cholesterol and with small LDL particles. AIM: To compare the effects of a 12-week treatment with micronized fenofibrate (200 mg) versus atorvastatin (10 mg) on apo CIII and lipoprotein-lipid levels including LDL size. METHOD: After a 4-week washout period, dyslipidemic patients were randomized to either micronized fenofibrate (n = 64) or atorvastatin (n = 72). RESULTS: Both fenofibrate and atorvastatin significantly decreased apo CIII levels by -0.03 +/- 0.03 versus -0.01 +/- 0.03 g/l respectively, and increased LDL size by 4.9 +/- 3.3 versus 1.8 +/- 2.9 A. Improvements in these parameters were significantly greater with fenofibrate (P < 0.0001). Significant relationships were found between changes in triglycerides and changes in apo CIII (r = 0.81 and r = 0.59, P < 0.0001) as well as between changes in LDL size and changes in apo CIII (r = -0.41 and r = -0.45, P < 0.001), in both fenofibrate and atorvastatin groups. respectively. CONCLUSION: The substantial reduction in apo CIII induced by micronized fenofibrate plays an important role in the greater effect of micronized fenofibrate than atorvastatin on plasma triglycerides and LDL size.

Adult↗

Deranged aortic intima-media thickness, plasma triglycerides and granulopoiesis in Sl/Sl(d) mice.

Studies were carried out to evaluate the impact of a high-fat dietary regimen on aortic wall thickness, peripheral blood leukocyte profile, and plasma cholesterol and triglyceride levels in the mast cell-deficient Sl/Sl(d) mouse. The results demonstrated that the mean aortic wall thickness of Sl/Sl(d) mice was significantly higher than their normal littermates, and were increased in both genotypes after a 17-day high-fat regimen. In comparison with normal littermates, Sl/Sl(d) genotypes had elevated levels of plasma triglycerides with normal levels of plasma cholesterol, and the high-fat diet markedly lowered the triglyceride levels. Total peripheral blood leukocytes, the monocyte and granulocyte counts, and hemoglobin levels were significantly lower in Sl/Sl(d) mice, although the number of lymphocytes, eosinophils and basophils were the same in both genotypes. Interestingly, the high-fat diet regimen elevated leukocyte counts and the number of monocytes and granulocytes in Sl/Sl(d) mice.

Animals↗

The atherogenic significance of an elevated plasma triglyceride level.

The importance of hypertriglyceridemia as an independent predictor of coronary artery disease (CAD) remains unsettled. Hypertriglyceridemia, with or without associated hypercholesterolemia, occurs more frequently in premature CAD subjects than does hypercholesterolemia alone. With univariate analysis, most studies show a positive correlation between plasma triglyceride (TG) level and risk for CAD, but with multivariate analysis plasma TG level is no longer an independent risk factor except in women and diabetics. Prospective studies have shown that subjects with a high LDL/HDL cholesterol ratio and a high plasma TG level have the highest risk for CAD. Hypertriglyceridemia signifies the presence of excess triglyceride-rich lipoproteins (TRL), including chylomicrons, VLDL, and their remnants. The question then becomes one of whether TRL are directly or indirectly involved in atherogenesis. TRL were thought to be too big to infiltrate the arterial wall, and histopathological studies have shown cholesterol but not triglyceride accumulation in the atherosclerotic plaque. However, there was a recent demonstration of undegraded VLDL and IDL in atherosclerotic plaques. Larger TRL may undergo hydrolysis on the arterial surface to become smaller particles before entry into the intima. Possible cellular pathways for the uptake of TRL by macrophages have been described. The smaller TRL (Sf 20-60), including postprandial chylomicron remnants, are believed to be the most atherogenic of all TRL particles. Because large amounts of TRL are produced in the postprandial period, atherogenesis involving TRL may be primarily a postprandial phenomenon. Once in the intima, TG may undergo hydrolysis, releasing free fatty acids and mono- and diacyl glycerol, accounting for the dearth of TG in atherosclerotic lesions. Particle for particle, VLDL delivers five times as much cholesterol as LDL does to the macrophage.

Angiography↗

Positive family history of coronary atherosclerosis and serum triglycerides may predict repeated coronary artery bypass surgery.

OBJECTIVE: Cardiovascular risk factor profile of patients in need of repeated coronary artery bypass surgery (redo CABG) seldom differ from patients having only single coronary artery bypass surgery (CABG). The aim of this study was to analyse the influence of positive family history for coronary artery disease in respect to redo CABG vs CABG in a case-control setting. DESIGN: One hundred and eighty four patients undergoing redo CABG between 1990-1998 were identified from the computed registry of the Department of Cardiothoracic Surgery in Tampere University Hospital. One hundred and eighty four age, gender and operation date matched patients with CABG were selected for control. RESULTS: According to chi-square analysis, positive family history for coronary artery disease was more common in Study group, 60.4% versus 49.5% (p<0.05). Preoperative systolic blood pressure was 135.5+/-1.4 mmHg versus 133.5+/-1.5 mmHg (ns), preoperative diastolic blood pressure was 81.2+/-0.8 mmHg versus 82.8+/-0.9 mmHg (ns), serum total cholesterol was 5.8+/-0.1 mmol/L versus 6.6+/-1.2 mmol/L and preoperative blood glucose was 5.6+/-0.2 mmol/L versus 5.3+/-0.2 mmol/L (ns) in Controls and Study group, respectively. However, serum triglyceride level was significantly higher in Study group 2.8+/-0.2 mmol/L versus 2.0+/-0.1 mmol/L (p<0.000). In regression analysis, only positive family history (OR=2.4; 95% CI=1.1-5.1; p<0,02) and high serum triglyceride level (>or=2 mmol/L, OR=1.6; 95% CI=1.2-2.2; p<0,02) were independent predictors for redo CABG. CONCLUSION: According to this study, positive family history for coronary atherosclerosis at the presence of high serum triglyceride level is significantly predicting the need for future redo CABG as compared with age, gender and operation time matched controls of CABG.

Biomarkers↗

Comparison of blood and brain toluene concentrations and circulating triglyceride levels resulting from acute and repeated exposures in rats.

Male Sprague-Dawley rats were exposed by inhalation to 2500 ppm toluene three hours per day, five days per week for three weeks. Blood and brain toluene concentration and circulating triglyceride levels were measured after one day, one week, two weeks and three weeks exposure. A consistent reduction in mean body weight gain was found in the toluene-exposed rats compared to controls as early as three days following initiation of exposure. During the second and third exposure week, the toluene-exposed rats exhibited marked salivation during the exposure periods. A dramatic decrease in brain and blood toluene levels occurred between the second and third exposure weeks. Also, an inverse relationship between circulating triglyceride levels and blood and brain toluene concentrations was found in the exposed rats. Plausible mechanisms for tolerance development and the inverse relationship to circulating triglycerides are offered including induction of hepatic mixed function oxidase activity and alterations in brain biomembrane lipid composition.

Animals↗

Intestinal triglyceride absorption in the rat. An electron microscopical study.

This report provides information on the morphology of fat absorption in rat intestinal epithelial cells. Three types of experiments were performed: (a) intubation of corn oil into fasted rats, (b) injection of physiological fatty-chyme prepared from fat-fed donor rats into ligated segments of jejunum of fasted animals, and (c) administration of electron-opaque particles in corn oil and markers given concurrently with the fat. These results support the hypothesis that fat is absorbed by selective diffusion of monoglycerides and fatty acids from micelles rather than by pinocytosis of unhydrolized triglycerides. Evidence is presented that the pits between the microvilli, previously believed to function in the transport of fat, are not involved in this process. Instead they appear to contribute their contents to lysosomes in the apical cytoplasm. Arguments are offered that the monoglycerides and fatty acids diffuse from the micelle while the latter is associated with the microvillous membrane of the absorptive cell. These micellar components penetrate the plasma membrane and diffuse into the cytoplasmic matrix where they encounter the SER. Triglyceride synthesis occurs in the SER and results in the deposition of fat droplets within its lumina. The synthesis of triglycerides and their sequestration into the SER establishes an inward diffusion gradient of monoglycerides and fatty acids.

Animals↗

Aged men and ischaemic heart disease: serum cholesterol and triglyceride levels.

Fasting serum cholesterol and triglyceride levels, and lipoprotein electrophoretic patterns have been investigated in 42 men aged 67-92 years (mean 79 years). Although all the cholesterol and the majority of the triglyceride levels were within the normal range for younger people, both were significantly greater (P < 0.001 and P < 0.01 respectively) in old men who had a clinical history of ischaemic heart disease than in the aged controls, whereas, in patients with dysrhythmia-ischaemia the cholesterol levels were raised (P < 0.05) but not the triglycerides. An abnormality of liporpotein profile was observed in 58% of patients with ischaemic heart disease; 7% of the controls; and 20% of patients having myocardial ischaemia associated with supraventricular dysrhythmia.

Age Factors↗

Quantification of plasma cholesterol and triglyceride levels in hypercholesterolemic subjects receiving ascorbic acid supplements.

In order to assess the possible effects of ascorbic acid on plasma cholesterol and triglyceride levels and plasma lipoprotein composition, nine hypercholesterolemic subjects were treated with oral ascorbic acid (4 g/day) for 2 months. The data demonstrate: 1) no significant change in plasma cholesterol or triglyceride levels; 2) no significant change in the cholesterol or triglyceride concentrations of the major lipoprotein classes; and 3) the unexpected appearance of extra pre-beta bands on lipoprotein electrophoresis by the end of the ascorbic acid treatment period.

Adult↗

Insulin, glucose and triglyceride relationships in obese African subjects.

Aspects of carbohydrate and lipid metabolism were studied in 50 nondiabetic African subjects living in Johannesburg. Twenty-six of them were overweight, invariably associated with a high-carbohydrate intake. In general, the obese group demonstrated significantly raised serum insulin levels, normal glucose tolerance, normal fasting serum triglycerides, and significantly elevated serum cholesterol concentrations. However, the degree of obesity was not significantly correlated with any of these metabolic variables--notably basal or stimulated insulin levels. This suggests that the obese state, per se, was not the major cause of the hyperinsulinemia, and that other factors influenced individual insulin responses or sensitivity. Inconsistently excessive dietary carbohydrate ingestion and an unusual degree of physical activity may have been important. A striking correlation emerged between fasting serum triglycerides and insulin concentrations (both basal and stimulated); the possibility that this reflects acceleration of hepatic triglyceride synthesis by insulin is discussed. The concept of obesity invariably producing insulin resistance and progressive compensatory hyperinsulinism may not apply in all environmental conditions.

Adult↗