Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In contrast to L-glutamine, lipid emulsions are routinely administered to patients receiving nutritional support. The provision of fat during intravenous feeding is essential, but the potentially toxic byproducts of fatty acid oxidation may have adverse metabolic consequences. In the present study, we have examined the effect of L-glutamine, an inhibitor of fatty acid oxidation, on the development of defective blood glucose regulation caused by a 48-hour infusion of 10% intralipid in rats. Male Sprague-Dawley rats (200-290 g) were anesthetized with sodium pentobarbital, the right femoral vein cannulated, and baseline blood samples were taken. Each rat was placed in a metabolic cage with access to water, in the presence or absence of rodent chow. Two hours after waking, the rats were infused with 10% intralipid with either saline (control), 2% L-glutamine, or 2% L-alanine. After 48 hours, all animals were sacrificed and blood samples were again obtained. The mean +/- SEM plasma glucose levels before and after lipid infusion at the rate of 1 mL/hr in control rats fed ad libitum, were 125 +/- 13 and 170 +/- 5 mg/dL (p < 0.01, n = 7). Similarly, plasma free fatty acids (FFA) in these animals rose from 0.74 +/- 0.11 to 1.34 +/- 0.32 mmol/L (p < 0.05). Plasma insulin levels also increased from 337 +/- 44 to 1278 +/- 88 pg/mL (p < 0.01). Reduction of intralipid dose infusion did not prevent insulin resistance characterized by hyperglycemia and hyperinsulinemia. However, addition of L-glutamine to the high-dose lipid infusion with chow feeding prevented changes in plasma glucose, insulin levels, and FFA but not triglyceride levels. Also, glutamine but not alanine supplementation in intralipid infused rats without chow feeding prevented changes in plasma glucose, insulin, and malondialdehyde levels. In conclusion, these data show that glutamine supplementation during intravenous lipid administration in rats prevents the development of impaired glucose regulation associated with hyperlipidemia.
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PMID:Effect of L-glutamine supplementation on impaired glucose regulation during intravenous lipid administration. 887 24

This study compared the effects of low and moderate intensity walking on postprandial lipemia, holding energy expenditure constant. Nine healthy normolipidemic subjects (5 men, 4 women; age 27.7 +/- 0.9, fasting, plasma triacylglycerol 0.95 +/- 0.18 mmol.l-1, mean +/- SEM) who were physically active but not endurance-trained undertook three trials, each over 2 d, in a balanced design. On the afternoon of day 1 they either refrained from exercise (Control), walked for 3 h at low intensity (Walk low, 32 +/- 1% VO2max), or walked for 1.5 h at moderate intensity (Walk moderate, 63 +/- 1% VO2max). The following morning, after a 12-h fast, they consumed a high-fat meal (1.3 g fat, 1.2 g carbohydrate, 0.2 g protein, 76 kJ energy per kg body mass). Blood and expired air samples were obtained before the meal and for 6 h afterward. Postprandial lipemia (total area under triacylglycerol concentration vs time curve) was lower than control after low intensity walking as well as after moderate intensity walking (both P < 0.05) but did not differ between the two walking trials (Control, 8.09 +/- 1.09 mmol.l-1 h; Walk low, 5.46 +/- 0.63 mmol.l-1.h; Walk moderate, 5.53 +/- 0.58 mmol.l-1.h). The increase in energy production following the test meal did not differ between trials, but fat oxidation was increased in the fasting and postprandial states for both walking trials, compared with control (P < 0.05).
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PMID:Reduction in postprandial lipemia after walking: influence of exercise intensity. 889 79

Repeated episodes of exaggerated postprandial lipemia may hasten the progression of atherosclerosis. The purpose of this study was to compare the lipemic response to a high-fat meal in trained and untrained women in the presence and absence of the acute effects of exercise. Nine endurance-trained and thirteen untrained women aged 40.4 +/- 3.3 and 43.8 +/- 4.3 y (mean +/- SD), with maximal oxygen uptake of 50.3 +/- 5.9 and 31.7 +/- 3.6 mL.kg-1.min-1, and a body mass index (kg/m2) of 22.2 +/- 0.9 and 22.9 +/- 2.3, respectively, underwent two trials, each over 2 d. Subjects did not exercise during the 2 d leading up to a trial. On day 1 they either walked for 90 min at 60% of maximal oxygen uptake (exercise), or refrained from exercise (control). On day 2 venous blood and expired air samples were obtained in the fasted state and for 6 h after consumption of a high-fat meal (1.70 g fat, 1.65 g carbohydrate, and 0.25 g protein/kg fat-free mass). Exercise decreased lipemia as determined by the mean (+/-SEM) area under the plasma triacylglycerol concentration versus time curve: trained, 6.96 +/- 0.48 compared with 4.87 +/- 0.33 mmol.h/L; untrained, 8.36 +/- 0.83 compared with 7.01 +/- 0.79 mmol.h/L (control and exercise trials, respectively, both P < 0.05). Lipemia differed significantly between groups in the presence of this acute effect of exercise but not in its absence. Exercise decreased insulinemia in trained women (543 +/- 25 compared with 433 +/- 24 pmol.h/L, P < 0.01) but had no effect in untrained women (592 +/- 34 compared with 585 +/- 47 pmol.h/L). Total oxidation of fat over the 6-h postprandial period was enhanced by exercise, and to a similar degree in each group of women.
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PMID:Acute effects of exercise on postprandial lipemia: a comparative study in trained and untrained middle-aged women. 902 40

To assess the long-term efficacy and use of fenofibrate together with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor ("statin") in the treatment of elevated levels of triglycerides and low-density lipoprotein (LDL) cholesterol, we conducted a study that compared a before- and after-case series. The study involved 80 patients with a diagnosis of combined hyperlipidemia and existing coronary artery disease (81% of patients) or outpatients with > or = 3 risk factors for coronary artery disease who had been receiving treatment at a tertiary care center. Fasting biochemical measures were obtained at baseline during monotherapy with a statin consisting of pravastatin 20 mg once daily or simvastatin 10 mg once daily (39 patients) or fenofibrate 300 mg once daily (41 patients), and during a 2-year period of combination therapy. This combination therapy comprised fenofibrate 300 mg once daily or micronized fenofibrate 200 mg once daily taken together with pravastatin 20 mg once daily (63 patients) or simvastatin 10 mg once daily (17 patients). The main outcome measures were: (1) absolute and percent change in total cholesterol, triglycerides, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol; (2) percentage of patients with alanine aminotransferase > or = 2x the upper limits of normal on any occasion; (3) percentage of patients with creatinine kinase > or = 3 times the upper limits of normal on any occasion; (4) absolute changes in alanine aminotransferase and creatinine phosphokinase; and (5) months on combination therapy. Patients receiving combination therapy had a mean total cholesterol (+/- standard error of the mean [SEM]) that was significantly decreased by 26+/-1%, triglycerides by 41+/-3%, and LDL cholesterol by 28+/-2%, and mean HDL cholesterol that was significantly increased by 22+/-6%. These changes correspond to mean absolute changes of total cholesterol: -75+/-5 mg/dL; triglycerides: -94+/-13 mg/dL; LDL cholesterol: -52+/-5 mg/dL; and HDL cholesterol: 5+/-1 mg/dL. During combination treatment, alanine aminotransferase increased by 2+/-2 U/liter (not significant) and creatinine phosphokinase decreased by 4+/-13 U/liter (not significant). During treatment, 8 patients (10%) had transitory isolated elevations in alanine aminotransferase levels > or = 2 times the upper limits of normal and 2 patients (2.5%) had an isolated and transitory elevation of creatinine kinase (> or = 3x but < 6x upper limits of normal) without associated muscle symptoms. Patient-years on combination therapy equaled 220.6 (average 2.06 years per patient). The results demonstrated that combination treatment with fenofibrate and low-dose simvastatin or pravastatin is generally safe and effective for the treatment of combined hyperlipidemia in patients with normal hepatic and renal function.
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PMID:Long-term efficacy and safety of fenofibrate and a statin in the treatment of combined hyperlipidemia. 952 16

The lipoprotein lipase (LPL) promoter -93T/G transition has previously been reported as having a triglyceride (Tg)-lowering effect, whereas the D9N variant has been shown to have a Tg-raising effect. These two variants were studied in 66 healthy subjects of Hispanic and 42 subjects of African-American origin, who had participated in a study of postprandial lipemia. While the allele frequency of the -93G was significantly different in the Hispanics and African Americans (0.09: 95% CI 0.04-0.13 and 0.28: 95% CI 0.19-0.38; P=0.0001, respectively), the N9 allele frequency was not different (0.06: 95% CI 0.02-0.1 and 0.05: 95% CI 0.002-0.093, respectively). Linkage disequilibrium between the -93T/G and D9N was highly significant in Hispanics (delta=0.67. P=0.0001), compared to delta=0.09 (NS) in African-Americans. In the combined group, compared to individuals with the common genotype (TT/DD; n=71) with fasting plasma Tg of 1.34 (+/-4.5% SEM) mmol/l, carriers of the G/D haplotype (TG/DD + GG/DD; n=25) had significantly lower plasma Tg levels of 1.08 (+/-10% SEM) mmol/l (P < 0.02). After the fat meal, compared to individuals with neither mutation, TT/DD, the effect of the G/D haplotype was to reduce significantly postprandial Tg (P < 0.036). Retinyl palmitate concentration at 5 hrs was significantly lower in G/D carriers than TT/DD individuals (P < 0.05). The lipid-raising effect of the N9 allele in carriers of the -93G (TG/DN + GG/DN) and effect on postprandial Tg clearance was not significant in this group. Thus carriers of the G/D haplotype have lower fasting plasma Tg and reduced alimentary lipemia. This allele may be associated with reduced risk of coronary artery disease.
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PMID:LPL promoter -93T/G transition influences fasting and postprandial plasma triglycerides response in African-Americans and Hispanics. 964 50

To determine whether high prevalence of small dense low-density lipoprotein (LDL) in non-insulin-dependent diabetes (NIDDM) with nephropathy is directly associated with kidney damage, we measured LDL particle size by non-denaturing 2-16% gradient polyacrylamide gel electrophoresis in non-diabetic patients with primary renal disease and compared the results to particle size in NIDDM patients with diabetic nephropathy. The average LDL particle diameter was significantly smaller in patients with diabetic nephropathy (245+/-3 A mean +/- SEM) compared to the controls (263+/-1 A), diabetics without nephropathy (257+/-2 A), patients with primary renal disease (254+/-2 A) or non-diabetic patients treated with hemodialysis (HD) (260+/-1 A). The incidence of small LDL (mean diameter is < or =255 A) was remarkably increased in diabetic nephropathy (67%) compared to diabetes without nephropathy (27%), patients with renal disease (24%), HD patients (15%) and controls (10%). LDL size in patients with primary renal disease was significantly smaller than those in controls. However, because there was an excellent correlation between LDL size and plasma triglyceride (TG) levels, when hypertriglyceridemic subjects (TG >1.7 mM) were excluded, no difference of LDL size was observed between the renal disease group (260+/-2 A) and the control group (264+/-1 A). On the other hand, even when hypertriglyceridemic subjects were excluded, LDL size was still smaller in diabetic nephropathy (250+/-4 A). We performed an oral fat load test in normotriglyceridemic subjects (fasting TG <1.7 mM) of control, diabetes with and without nephropathy and primary renal disease. The TG responses in plasma and TG-rich-lipoprotein (TRL) (d <1.006) after the oral fat load were significantly greater in NIDDMs with nephropathy compared to controls or NIDDMs without nephropathy, while such a marked postprandial lipemia was not observed in patients with primary renal disease. In these fasting normotriglyceridemic subjects, LDL size was significantly inversely correlated with postprandial TG responses, which is totally independent from fasting TG levels. These results suggest that high prevalence of small dense LDL in NIDDM patients with nephropathy is not directly associated with kidney damage. Postprandial lipemia may play an important role in reducing LDL particle size in these patients.
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PMID:High prevalence of small dense LDL in diabetic nephropathy is not directly associated with kidney damage: a possible role of postprandial lipemia. 986 40

A single session of exercise several hours before a high-fat meal reduces postprandial lipemia. The purpose of the present study was to test the hypothesis that this effect is independent of substrate metabolism during exercise. Twelve men aged 21 to 36 years underwent three oral fat tolerance tests with intervals of at least 1 week. On one occasion, only activities of daily living were allowed the preceding day (control). On the other two occasions, subjects ran on a treadmill for 90 minutes on the afternoon preceding the fat tolerance test; 90 minutes before running, they ingested either acipimox, an inhibitor of lipolysis in adipose tissue, or placebo. Acipimox abolished the increase in the nonesterified fatty acid (NEFA) concentration observed during the run after placebo and reduced lipid oxidation (placebo, 37 +/- 7 g; acipimox, 21 +/- 3 g; P < .05, mean +/- SEM), but had no effect on gross energy expenditure (placebo, 4.86 +/- 0.20 MJ; acipimox, 4.83 +/- 0.18 MJ). Before each of the three fat tolerance tests, subjects reported to the laboratory after an overnight fast. Blood samples were obtained in the fasted state and for 6 hours after consumption of a high-fat meal (per kilogram of body mass: 1.2 g fat, 1.2 g carbohydrate, and 61 kJ energy). Plasma concentrations of NEFA were higher postprandially with acipimox, compared with control and placebo (P < .05), as were glucose concentrations measured over the first 4 hours. The insulin response to the meal was lower in placebo compared with control and acipimox (P < .05). Despite these counterregulatory responses, postprandial lipemia was reduced to the same degree (compared with control, P < .05) by exercise preceded by acipimox and by exercise preceded by placebo (area under the plasma triacylglycerol concentration v time curve: control, 8.77 +/- 1.17 mmol/L x 6 h; placebo, 6.95 +/- 0.97 mmol/L x 6 h; acipimox, 6.81 +/- 0.81 mmol/L x 6 h). These findings suggest that some factor other than the nature of the metabolic substrate used during exercise determines the attenuating effect of prior exercise on postprandial lipemia.
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PMID:The reduction in postprandial lipemia after exercise is independent of the relative contributions of fat and carbohydrate to energy metabolism during exercise. 1002 90

Hypopituitarism is associated with hyperlipidemia, the mechanisms of which are not fully known. One possible mechanism is an increased hepatic secretion of very-low-density lipoprotein (VLDL) apolipoprotein B100 (apo B100). To investigate this, 13 hypopituitary patients (seven women and six men; age, 46 +/- 3 years [mean +/- SEM]; body mass index [BMI], 29 +/- 2 kg/m2) and 13 matched controls (seven women and six men; age, 43 +/- 3 years; BMI, 28 +/- 2 kg/m2) were investigated in a stable-isotope study. [1-(13)C]leucine (1 mg/kg body weight) was administered, followed by a continuous 6-hour infusion of [1-(13)C]leucine (at a rate of 1 mg/kg/h). Patients had a similar fractional secretion rate (FSR) of VLDL apo B100 versus controls (0.37 +/- 0.05 v 0.38 +/- 0.06 pools/h, respectively), but they had a significantly larger pool size (3.4 +/- 0.3 v 1.9 +/- 0.3 mg/kg) and higher absolute secretion rate ([ASR] 27.8 +/- 2.9 v 16.0 +/- 2.5 mg/kg/d). The increase in hepatic VLDL production may explain the lipid abnormalities found in hypopituitarism. Fasting circulating nonesterified fatty acids (NEFAs) were decreased in the patients (284 +/- 26 v 664 +/- 92 micromol/L, P < .001) despite the increase in VLDL secretion. An inverse relationship was observed between the NEFA level and VLDL apo B100 FSR in the patients (r(s) = -.85, P < .005).
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PMID:Very-low-density lipoprotein apolipoprotein B100 kinetics in adult hypopituitarism. 1045 74

Plasma concentrations of lipoprotein (a) [Lp(a)] are increased in patients on renal replacement therapy. Lipoprotein (a) is increasingly being recognized as an independent cardiovascular risk factor. In an effort to explore the mechanism for elevation of Lp(a) in patients on dialysis we have performed turnover studies of Lp(a) with radioactive iodine. Lp(a) was isolated from 1 patient on hemodialysis (HD) and 1 patient on continuous ambulatory peritoneal dialysis (CAPD); the protein was labeled with 125I and returned to each patient. Lipoprotein (a) was subsequently isolated from the patients over a 15-day period and the decay of the specific radioactivity of Lp(a) was used to determine the fractional catabolic rate (FCR), which was 0.27 (pool/day) for the HD patient and 0.28 (pool/day) for the CAPD patient. These rates are indistinguishable from those measured in 4 patients with hypercholesterolemia (0.29, SEM = 0.01) and in 4 other familial hypercholesterolemic patients (0.29, SEM = 0.02) studied previously using the same method by Knight et al. (7). We found no difference in the FCR of patients on dialysis when compared to patients with hyperlipidemia and normal renal function. Increased plasma concentration of Lp(a) in our patients on renal replacement therapy is not due to decreased catabolism, but is caused by increased synthesis.
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PMID:Mechanism for elevated plasma lipoprotein(a) concentrations in patients on dialysis: turnover studies. 1064 29

Adult hypopituitarism is associated with hyperlipidemia, mainly due to an increase of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels. Recent studies have shown that such patients exhibit increased hepatic secretion of VLDL apolipoprotein B100 (VLDL apo B100). To examine the effects of growth hormone (GH) replacement on VLDL apo B100 turnover, 13 GH-deficient hypopituitary patients (8 women and 5 men; aged 47 +/- 3 years, mean +/- SEM; body mass index [BMI], 30 +/- 2 kg/m2) entered a double-blind placebo-controlled study for 6 months (GH 0.125 IU/kg/wk for 4 weeks, and then 0.25 IU/kg/wk). GH was subsequently used in all patients for a further 6 months. A 6-hour [1-13C] leucine infusion was administered at baseline and at 6 months. The secretion rate of VLDL apo B100 was derived by kinetic analysis following quantitation of isotopic enrichment by gas chromatography/mass spectrometry. The GH-treated group (6 patients) demonstrated a similar fractional secretion rate (FSR) for VLDL apo B100 at 0 and 6 months. The pool size and absolute secretion rate (ASR) also were unaffected significantly by GH therapy. No significant changes were observed in the placebo group (7 patients). Treatment with GH for 6 months caused an increase in the high-density lipoprotein (HDL) cholesterol concentration (13 patients, 1.27 +/- 0.13 v 1.16 +/- 0.10 mmol/L, respectively, P = .05), whereas total cholesterol and triglyceride concentrations did not change. Nonesterified fatty acids (NEFAs) increased during GH therapy (471 +/- 43 micromol/L at 6 months v 349 +/- 49 micromol/L at baseline, P < .0005). The data suggest that GH does not affect VLDL apo B100 turnover in a significant way.
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PMID:Effects of growth hormone treatment on very-low density lipoprotein apolipoprotein B100 turnover in adult hypopituitarism. 1083 Nov 63


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