Effect of n-3 fatty acids on metabolism of apoB100-containing lipoprotein in type 2 diabetic subjects.

The effect of long-chain n-3 PUFA on the metabolism of apoB100-containing lipoprotein in diabetic subjects is not fully understood. The objective of the present study was to determine the effect of a daily intake of 1080 mg EPA and 720 mg DHA for diabetic subjects on the kinetics of apoB100-containing lipoprotein in the fasting state. A kinetic study was undertaken to determine the mechanisms involved in the effects of n-3 fatty acids in terms of a decrease in triacylglycerol level in type 2 diabetic patients. We have studied the effect of fish oils on the metabolism of apoB100 endogenously labelled by [5,5,5-2H3]-leucine in type 2 diabetic patients in the fasting state. The kinetic parameters of apoB100 in VLDL, intermediate-density lipoprotein and LDL were determined by compartmental modelling in five diabetic subjects before and 8 weeks after n-3 fatty acid treatment. Treatment did not change the plasma cholesterol level (0.801 (sd 0.120) v. 0.793 (sd 0.163) mmol/l) but lowered the plasma triacylglycerol level (1.776 (sd 0.280) v.1.356 (sd 0.595) mmol/l; P < 0.05). Treated patients showed a decrease in VLDL apoB100 concentration (0.366 (sd 0.030) v.0.174 (sd 0.036) g/l; P < 0.05) related to a decrease in VLDL 1 production (1.49 (sd 0.23) v.0.44 (sd 0.19) mg/kg per h; P < 0.05) and an increase in the VLDL conversion rate (0.031 (sd 0.024) v.0.052 (sd 0.040) per h; P < 0.05), with no change in fractional catabolic rates. Treatment led to a higher direct production of intermediate-density lipoprotein (0.02 (sd 0.01) v.0.24 (sd 0.12) mg/kg per h; P < 0.05). In conclusion, the present study, conducted in the fasting state, showed that supplementation with n-3 fatty acids in type 2 diabetic patients induced beneficial changes in the metabolism of apoB100-containing lipoprotein.

Effects of atorvastatin on high-density lipoprotein apolipoprotein A-I metabolism in dogs.

BACKGROUND: The mechanisms involved in the decline of high-density lipoprotein (HDL) levels at a higher dose of atorvastatin have not yet been elucidated. We investigated the effects of atorvastatin on HDL-apolipoprotein (apo) A-I metabolism in dogs, a species lacking cholesteryl ester transfer protein activity. MATERIALS AND METHODS: Seven ovariectomized normolipidaemic female Beagle dogs underwent a primed constant infusion of [5,5,5-(2)H(3)] leucine to determine HDL-apo A-I kinetics before and after atorvastatin treatment (5 mg kg(-1) d(-1) for 6 weeks). Plasma lipoprotein profiles, activity of HDL-modifying enzymes involved in reverse cholesterol transport and hepatic scavenger receptor class B type I (SR-BI) expression were also studied. RESULTS: Atorvastatin treatment decreased HDL-cholesterol levels (3.56 +/- 0.24 vs. 2.64 +/- 0.15 mmol L(-1), P < 0.05). HDL-triglycerides were not affected. HDL-phospholipids levels were decreased (4.28 +/- 0.13 vs. 3.29 +/- 0.13 mmol L(-1), P < 0.05), as well as phospholipids transfer protein (PLTP) activity (0.83 +/- 0.05 vs. 0.60 +/- 0.05 pmol microL(-1) min(-1), P < 0.05). Activity of lecithin: cholesterol acyl transferase (LCAT), hepatic lipase (HL) and SR-BI expression did not change. HDL-apo A-I absolute production rate (APR) was higher after treatment (twofold, P < 0.05) as well as fractional catabolic rate (FCR) (threefold, P < 0.05). This resulted in lower HDL-apo A-I levels (2.36 +/- 0.03 vs. 1.55 +/- 0.04 g l(-1), P < 0.05). Plasma lipoprotein profiles showed a decrease in large HDL(1) levels, with lower apo A-I and higher apo E levels in this subfraction. CONCLUSIONS: Although a high dose of atorvastatin up-regulated HDL-apo A-I production, this drug also increased HDL-apo A-I FCR in dogs. This effect could be explained by a higher uptake of apo E-enriched HDL(1) by hepatic lipoprotein receptors.

Effect of dietary omega-3 fatty acids on high-density lipoprotein apolipoprotein AI kinetics in type II diabetes mellitus.

The effect of a dietary fish oil supplementation on metabolism of HDL was studied in type II diabetes mellitus. Endogenous labeling of HDL-apo AI was performed using a 14 h primed infusion of D3-leucine in five diabetic patients before and 2 months after treatment with maxEPA(R). Isotopic enrichment curves were analyzed using a monoexponential function. After treatment, plasma cholesterol level remained unchanged (205.4+/-41.9 vs. 206.8+/-30.7 mg/dl, NS), whereas plasma triglycerides were decreased (155.4+/-67.9 vs. 202.6+/-32.2 mg/dl, P=0.06). Plasma apo AI was similar under maxEPA(R) (116.0+/-25.6 vs. 111.8+/-25.4 mg/dl, NS), and HDL-cholesterol and HDL-triglycerides were also not markedly changed (30.2+/-10.0 vs. 27.1+/-10 mg/dl, and 15.3+/-9.8 vs. 19.2+/-10.4 mg/dl, NS). HDL-apo AI fractional catabolic rate (FCR) and absolute production rate (APR) were significantly decreased after treatment with maxEPA(R) (0.27+/-0.09 vs. 0.37+/-0.08 pool day, P<0.05, and 12.1+/-2.8 vs. 16.1+/-3.3 mg/kg per day, P<0.05). These findings showed an effect of maxEPA(R) on kinetics of apolipoprotein AI in type II diabetes mellitus, probably linked to changes in plasma triglyceride level.

Increased cholesteryl ester transfer activity in plasma from analbuminemic patients.

Hypercholesterolemia associated with analbuminemia, an inherited disease manifesting low plasma albumin concentration, is characterized by enhanced LDL cholesterol levels and reduced HDL cholesterol levels. In addition, compared with normal counterparts, the esterified cholesterol:triglyceride ratio tends to be higher in analbuminemic apoB-containing lipoproteins and lower in analbuminemic HDL. The aim of the present study was to investigate the mechanism that may account for the association of a hypoalbuminemic state with alterations in the concentration and composition of plasma lipoprotein fractions. To this end, endogenous cholesterol esterification activity, phospholipid transfer activity, and cholesteryl ester transfer activity were measured in total plasma from three analbuminemic patients and five control subjects. Whereas endogenous cholesterol esterification and phospholipid transfer rates were not significantly affected in analbuminemia, the transfer of radiolabeled cholesteryl esters from HDL toward apoB-containing lipoproteins was constantly higher in analbuminemic plasmas than in normal control plasma (473.6+/-107.3% x h(-1) x mL(-1) versus 227.5+/-84.0% x h(-1) x mL(-1), respectively; P=.036). The rise in cholesteryl ester transfer protein (CETP) activity in analbuminemic plasma was due to a significant increase in the transfer of radiolabeled cholesteryl esters toward LDL but not toward the triglyceride-rich lipoproteins. The CETP mass was higher in analbuminemic patients than in control subjects, but the difference did not reach the significance level (5.18+/-0.82 mg/L versus 3.13+/-1.19 mg/L respectively; P=.07). Since abnormally elevated nonesterified fatty acid (NEFA) levels were shown to be associated with analbuminemic lipoproteins, mostly LDL, the direct role of lipoprotein-bound NEFA in enhancing CETP activity was suspected. In support of this view, supplementation of total plasmas with fatty acid-poor albumin was shown to reduce CETP activity to a significantly greater extent in analbuminemic plasmas than in normal control plasma. It is concluded that hyperlipidemia associated with the hypoalbuminemic state can relate, at least in part, to the combined effect of CETP and NEFA in promoting the transfer of cholesteryl esters from the antiatherogenic HDL toward the proatherogenic apoB-containing lipoproteins.

Comparative study of the acute effects of resistant starch and dietary fibers on metabolic indexes in men.

The effect of ingestion of the same amount (30 g) of a resistant starch (lintner) and cellulose on energy expenditure (EE), colonic fermentation (breath-hydrogen test), and blood glucose, insulin, and free fatty acid (FFA) concentrations were compared in seven healthy volunteers in a first experiment. In a second experiment the same indexes were measured in six healthy volunteers after the ingestion of diets composed of 50 g glucose alone or mixed with 30 g lintner, or cellulose, or pectin. In the first experiment no differences between lintner and cellulose were observed on the measured indexes. The notable difference was the increased apparent colonic fermentation with lintner after 6 h. In experiment 2, although insulin response was significantly lower in the pectin-added diet, the results obtained with the four different diets were not significantly different. The metabolic characteristics of lintner were closer to cellulose than to pectin. In conclusion, the acute effect of the ingestion of a resistant starch (lintner) on the measured metabolic indexes is similar to that of a known insoluble fiber--cellulose.

Determination of alpha-tocopherol in plasma, platelets and erythrocytes of type I and type II diabetic patients by high-performance liquid chromatography.

Vitamin E (alpha-tocopherol) concentrations of plasma, platelets and erythrocytes were determined by HPLC in insulin-dependent (type I) and age-matched non-insulin-dependent (type II) diabetic patients and in two control groups. Plasma alpha-tocopherol levels were significantly increased in diabetic patients compared to control groups. Platelet and erythrocyte alpha-tocopherol levels were not significantly different in type I and type II diabetics as compared to their respective control groups, but differed from one another. Plasma vitamin E concentrations showed a significant correlation with plasma cholesterol and apoprotein B concentrations in different groups. The alpha-tocopherol/cholesterol and alpha-tocopherol/apoprotein B ratios in plasma were higher in diabetic patients, as were triglyceride contents. Platelet vitamin E levels were not significantly correlated with plasma concentrations. These findings suggest that vitamin E activity is altered in diabetic patients but that no diet supplementation seems necessary.