Cardiac performance and plasma lipids of omega-3 fatty acid-treated streptozocin-induced diabetic rats

We studied the effect of omega-3 fatty acid (omega 3FA) treatment on plasma lipids and cardiomyopathy in the diabetic rat. The omega 3FA preparation used was Promega. Male Wistar rats (250-275 g) were rendered diabetic by streptozocin (STZ; 55 mg.kg-1). Nondiabetic control rats received the vehicle alone. Two weeks after STZ or vehicle injection, control and diabetic rats were randomly assigned to either a treated or untreated group. Promega was administered at a dose of 0.5 ml.kg-1.day-1 by oral gavage for 4 wk, after which the rats were decapitated, plasma collected, and isolated working heart performance studied. Promega treatment did not affect plasma glucose, triglyceride, or cholesterol concentrations of either the control or diabetic rats. Cardiac performance was assessed by measuring the left ventricular response to changing left atrial filling pressures (7.5-20 cm H2O). The treatment had no effect on peak left ventricular developed pressure (LVDP) or maximal rate of change of left ventricular pressure during systole (+dP/dtmax) or diastole (-dP/dtmax) in the nondiabetic control rats. LVDP and +/- dP/dt were significantly improved (P less than .05) in the treated diabetic rats compared with untreated diabetic rats, although cardiac performance did not improve to the nondiabetic level. Cardiac sarcoplasmic reticulum (SR) calcium transport activity was not affected by the treatment in the control rats but was significantly improved (P less than .05) in the treated diabetic rats. These data suggest that omega 3FA treatment partially blocks the development of experimental diabetic cardiomyopathy, possibly by affecting SR calcium transport activity.     

Whole-plasma and high-density lipoprotein subfraction surface lipid composition in IDDM men

To determine whether compositional abnormalities are present in high-density lipoprotein (HDL) in patients with insulin-dependent diabetes mellitus (IDDM) that might negate its putatively protective cardiovascular effects, we studied the plasma lipoproteins of 12 men with varying degrees of clinical control (mean fasting glucose 193 +/- 10 mg/dl, mean glycoalbumin greater than 73% above control mean). The diabetic patients' basal plasma triglyceride, total- and free- (unesterified) cholesterol, HDL cholesterol (HDL-chol), and apolipoprotein AI, AII, and B concentrations were similar to those of control subjects, but the free-cholesterol-to-lecithin ratio, a new index of cardiovascular disease risk, was significantly increased in their plasma (0.97 +/- 0.14 vs. 0.88 +/- 0.07, P less than .02) and their very-low-density lipoprotein (VLDL)-low-density lipoprotein (LDL) subfraction (1.50 +/- 0.51 vs. 1.08 +/- 0.15, P less than .005). Although HDL2-chol was similar in diabetic and control groups, the HDL2-chol-to-free-cholesterol ratio (diabetic vs. control, 4.64 +/- 1.7 vs. 1.96 +/- 1.0 mumol/ml, P less than .025) and the sphingomyelin-to-lecithin ratio (0.23 +/- 0.08 vs. 0.20 +/- 0.09, P less than .025) were both significantly increased in the IDDM group. HDL3-chol was higher in the IDDM than in the control subjects (diabetic vs. control, 38.6 +/- 5.2 vs. 32.7 +/- 2.7 mg/dl, P less than .005). In contrast to whole plasma and the VLDL + LDL subfraction, the free-cholesterol-to-lecithin ratio of IDDM and control HDL subfractions were similar.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of clofibrate on plasma lipids and high-density lipoprotein levels in renal allograft recipients.

Thirteen successfully transplanted renal patients with normal and elevated plasma lipids were treated as out-patients for two-month intervals with placebo and clofibrate (2 g/day) and whole plasma and lipoprotein triglyceride and cholesterol concentrations were measured. With clofibrate treatment, plasma triglyceride (194 +/- 11 to 157 +/- 10 mg/100 ml; P less than .01) and cholesterol (242 +/- 8 to 212 +/- 8 mg/100 ml; P less than .002) concentrations both decreased significantly despite the continued administration of stable immunosuppressive doses of prednisolone. While the absolute changes in cholesterol in the low and high-density lipoprotein classes varied considerably following clofibrate administration, the ratio of cholesterol in the low and high-density lipoproteins fell from 3.8 to 3.3. This theoretically beneficial anti-atherogenic effect was significant (P less than .01) in male allograft recipients only. These findings indicate that clofibrate treatment favorably influences the cardiovascular risk posed by both qualitative and quantitative disturbances in lipoprotein transport following successful renal allografting.     

Effect of fish oil concentrate on lipoprotein composition in NIDDM

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with elevated very-low-density lipoprotein (VLDL) triglyceride concentrations and abnormalities of low-density lipoprotein (LDL) composition. Because fish oil supplementation may favorably affect lipid and lipoprotein concentrations in nondiabetic subjects, we determined the effect of fish oil concentrate on plasma lipids and lipoprotein composition in patients with NIDDM. Dietary-supplementation 1-mo periods of 4.0 and 7.5 g of omega-3 fatty acids in fish oil were compared with a placebo of 12 g safflower oil by use of a single-blind crossover design. Medications, including antidiabetic therapy, were continued through the study. Compared with safflower oil treatment, fish oil supplementation resulted in a significant reduction of total plasma triglycerides of 24% at the 4-g dose and a larger reduction of 39% at the 7.5-g dose. These decreases were due to similar reductions in VLDL triglycerides. LDL cholesterol levels were mildly elevated, but a larger 20% increase in LDL apolipoprotein B (apoB) concentration was observed. During supplementation with the fish oil concentrate, the LDL cholesterol-to-apoB ratio was significantly reduced when compared with pretreatment values, but not when compared with safflower oil treatment. High-density lipoprotein (HDL) cholesterol and plasma apoA1 levels were not significantly changed during fish oil treatment. At the 7.5-g dose, fasting glucose and glycohemoglobin levels increased by 20 and 12%, respectively, but were unchanged at the lower level of supplementation. Thus, in NIDDM patients, dietary supplementation with omega-3 fatty acids induces a reduction in total plasma and VLDL triglyceride levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of cyclosporine on plasma lipids and modification with dietary fish oil

Hyperlipidemia is an identified risk factor for atherosclerosis in patients following renal transplantation that may be related to previous uremia and various drugs including steroids. Recent evidence has suggested that treatment with cyclosporine may be an independent risk factor for development of hyperlipidemia in some patients. Twenty-four Sprague Dawley rats were given CsA at 30 mg/kg by gavage for 28 days in 1 ml of olive oil or fish oil vehicle, and compared with controls receiving just vehicle. Increases of both triglyceride (233.6%) and cholesterol (50.9%) were observed in olive oil/CsA animals (P less than .01), with no significant change noted with either vehicle alone. An increase of triglyceride from baseline was observed with fish oil/CsA (119%) (P less than .01) but was significantly less than the increase with olive oil/CsA animals (P less than .05). No increase in cholesterol was found in CsA-treated rats using the fish oil vehicle. The mechanisms leading to hyperlipidemia with four weeks of CsA administration in these rats are unknown, but may be related to altered hepatic synthesis. CsA levels were lower in fish oil-treated animals, possibly explaining the difference noted in lipid levels--or, alternatively, reduction of plasma lipoproteins may have altered drug kinetics and CsA binding. This work emphasizes a need for further study of lipids in CsA-treated patients, and advises some caution in the use of lipoprotein-reducing agents in patients using CsA without consideration of the possible effect on free drug levels.     

Postheparin plasma lipoprotein lipase and hepatic lipase in diabetes mellitus. Relationship to plasma triglyceride metabolism.

The activity of two triglyceride lipases was determined by an immunochemical method in the postheparin plasma of 60 diabetic patients and of 47 age- and sex-matched nondiabetic control subjects. The results were related to the type of diabetes, to plasma triglyceride and insulin concentrations, to removal of exogenous fat from the blood, and to turnover of VLDL-triglycerides . The mean postheparin plasma lipoprotein lipase (LPL) activity was decreased by 44 per cent (p less than 0.001) in patients with untreated ketotic diabetes and by 20 per cent (p less than 0.01) in patients with untreated mild to moderate nonketotic early-onset diabetes. Insulin treatment of ketotic diabetes resulted in a rapid increase in the activity of LPL and decrease in serum triglycerdie level, whereas sulfonylurea treatment of non-insulin-requiring diabetics did not significantly influence the enzyme activity. In insulin-treated chronic diabetics the average postheparin plasma LPL activity was not different from that of nondiabetic controls, but some of these patients had high LPL values. In normolipidemic maturity-onset-type diabetics the LPL activity was within normal range, but in those having hypertriglyceridemia the average LPL value was decreased by an average of 26 per cent (p less than 0.01). The LPL activity showed a significant negative correlation with the logarithm of serum triglyceride concentration (r = -0.62) and a positive correlation with fractional removal of Intralipid (r = +0.64) and fractional turnover of V triglyceride (r = +0.40). The activity of LPL was correlated to basal plasma insulin concen tration in the insulin-deficient diabetes r = +0.34) but not in patients with maturity-onset-type diabetes. The hepatic lipase (HL) activity of postheparin plasma was similar in diabetes and controls, with the exception of hypertriglyceridemic maturity-onset diabetics, who had higher mean HL activity than the corresponding control group (p greater than 0.01). The activity of HL was not related to triglyceride removal but showed a significant correlation to VLDL-triglyceride production rate. On the basis of these results it seems that a deficiency of LPL accounts for a great deal of the elevation of serum triglyceride in insulin-deficient human diabetes but has a smaller role in the pathogenesis of the hypertriglyceridemia that is associated with maturity-onset diabetes. The latter abnormality is caused mainly by an increased secretion of triglycerides into the blood even though a decreased LPL may contribute to development of hyperlipemia in cases with gross elevation of serum triglycerides.     

Study on the inhibitory effect of uremic plasma on lipoprotein lipase.

An investigation was undertaken to determine which plasma factors from normal controls and patients with chronic renal failure (CRF) exert have inhibitory effects on the activity of lipoprotein lipase (LPL) purified from heparinized human plasma by using an accurate LPL assay system. Inhibitors of LPL were found to be present in the plasma. The inhibition of the LPL activity was significantly greater in CRF patients than in normal controls. Following hemodialysis (HD), the same concentration of uremic plasma led to less inhibition. The inhibitors existed only in lipoprotein deficient plasma (LPDS), which demonstrated an LPL-inhibitory activity at extremely high concentrations with a significant difference between the patients and normal controls. There was no difference between the two groups at low concentrations. A specific inhibitory effect on LPL in LPDS was noted in the 7S and 4S fractions separated by gel filtration employing Sephacryl S-200 column chromatography. The inhibitory effect of the 7S fraction was found to be dependent on the concentration, and the difference between the two groups was similar to that for LPDS. The results obtained in the present study suggest that the plasma from CRF patients exhibited a strong inhibitory action on the LPL activity as compared to the plasma from normal controls, and the inhibitory action was due primarily due to poor excretion of dialyzable inhibitors.     

Dissociation between plasma triglyceride concentration and tissue lipoprotein lipase deficiency in insulin-deficient rats

Insulin deficiency was produced by streptozotocin in young (5-6 wk old) male rats, and measurements were made of plasma triglyceride and glucose concentrations and of lipoprotein lipase (LPL) activity of adipose tissue (epididymal) and muscle (gastrocnemius and soleus). Rats with streptozotocin-induced diabetes underwent a significant reduction in adipose tissue LPL activity (both total and heparin releasable), but the fall in LPL activity in these rats bore little relationship to their rise in plasma triglyceride concentration. Furthermore, muscle LPL activity was essentially unchanged in diabetic rats. Qualitatively similar changes were observed when measurements were made at either 8 a.m. (after the normal evening access to food) or 2 p.m. (6 h after food withdrawal). It is concluded that the hypertriglyceridemia that occurs secondary to insulin deficiency is not a simple function of decreased tissue LPL activity.     

Disorders of serum omega-3 fatty acid composition in dialyzed patients,and their associations with fat mass

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular mortality. Lipid disorders, a constant feature of CKD, might contribute to this state. The aim of this study was to evaluate n-3 polyunsaturated fatty acids (PUFA) composition in CKD patients treated with dialysis, in comparison to the general population and to assess possible associations between the n-3 PUFA profile and anthropometric variables. Thirty-three prevalent dialysis patients were studied and compared with an age- and sex-adjusted control group of 22 patients. Fatty acid composition in serum was analyzed by gas chromatography with a mass spectrometer detector (GC-MS) and anthropometric measures were assessed by bioimpedance spectroscopy. The fatty acid profile of dialyzed patients was characterized by a significantly lower percentage content of n-3 PUFA. For α-linolenic acid (ALA), it was 0.21?±?0.09% in dialysis patients versus 0.33?±?0.11% in the control group (p?p?p?r?=?.48 (p?r?=?.40 (p?相似文献   

A study on the fatty acid composition of the plasma lipoprotein in patients with fractures

Although the etiology of post-traumatic fat embolization still remains obscure, various concepts as to the pathophysiology of the syndrome have emerged in recent years. Extensive studies have indicated that trauma and surgical stress cause remarkable alterations in lipid metabolism. In the following study designed to characterize this situation more fully, the author has analyzed the changes of fatty acid composition of triacylglycerol, phospholipid and cholesterol ester in the circulating plasma lipoprotein of the patient with fractures. Materials and Methods: Ten patients who sustained one or more fractures without chest injury between age 9 and 79 years and seven healthy human subjects as control were selected for study. Blood samples were withdrawn into EDTA-treated syringes from patients after overnight fast at intervals of 2, 3, 4, 5 and 14 days after injury. Lipoprotein fractions (very low density lipoprotein: VLDL, low density lipoprotein: LDL, high density lipoprotein: HDL, and very high density lipoprotein: VHDL) were prepared by the method of ultracentrifugation. Lipids were extracted from the lipoprotein fractions according to the procedure of Folch. Lipids separation and purification were carried out by one-dimension thin-layer chromatography. The purified lipids were methylated with BF3-methanol complex and the fatty acid composition of each lipid fraction was analyzed by gas-liquid chromatography. Results: In the blood samples of normal subjects and patients, myristic, palmitic, palmitoleic, stearic, oleic and linoleic acids (C14: 0, C16: 0, C16: 1, C18: 0, C18: 1 and C18: 2) were the principal fatty acids and these fatty acids were all altered after injury except C14: 0 and C18: 2. The distribution of fatty acids in VLDL-TL was especially altered from the 3rd to 5th hospital day. Stearic acid derived from VLDL-PL was decreased and C18: 1 derived from VLDL-TG was increased. Of the ten patients there were greater changes in those with the femoral fracture. In LDL-TL, the distribution of fatty acids was also altered, and C18:1 derived from LDL-TG was increased. In fatty acid composition of HDL-TL, C16: 0 derived from HDL-PL and C18: 1 derived from HDL-TG were increased and C18: 0 derived from HDL-PL was decreased. In fatty acid composition of VHDL-TL, C16: 1 derived from VHDL-TG was increased.     

雷洛昔芬对绝经后妇女同型半胱氨酸及血脂的影响

目的观察雷洛昔芬(RLX)对绝经后妇女同型半胱氨酸及血脂的影响。方法采用随机、双盲、安慰剂对照研究,对62例绝经后妇女分为试验组(n=32)和安慰剂组(n=30),分别给予RLX 60 mg/d及安慰剂,共12个月。结果RLX组用药6个月前后同型半胱氨酸无明显变化,用药12个月时明显降低,与安慰剂组比较有显著性差异(P<0.05);RLX组用药12个月总胆固醇、低密度脂蛋白胆固醇显著降低(P<0.01),高密度脂蛋白胆固醇和甘油三酯则无明显变化。结论RLX可降低绝经后妇女同型半胱氨酸水平,降低血清总胆固醇、低密度脂蛋白胆固醇水平。     

Life stress,emotional reactivity and their relation to plasma lipids in employed women

The few studies exploring the association of chronic life stress with plasma lipid levels have yielded inconsistent results. However, these levels have been more consistently associated with the individual's state of emotional arousal. This study examined whether women prone to sustained emotional arousal in the face of emotional events would manifest elevated plasma lipid levels when exposed to chronic life stress. Subjects were 941 employed women free of medical factors potentially affecting plasma lipids. Proneness was measured by the emotional reactivity (ER) scale. Multiple regression analyses indicated that lipid levels were related neither to life stress nor to the life stress × ER interaction. However, ER was negatively related to HDL (p = 0.041) and positively to cholesterol/HDL (p = 0.006) and LDL (p = 0.063), even after adjusting for several possible confounders. Furthermore, women who scored in the upper third of the ER scale showed the highest proportion of ‘high-risk’ LDL and cholesterol/HDL levels. These findings indicate that it is not reported life stress, but the propensity to experience sustained emotional arousal that is associated with chronic plasma lipid elevation.