Acute inhibition of hepatic lipase and increase in plasma lipoproteins after alcohol intake

Chronic alcohol intake is associated with an increase in fasting plasma high density lipoproteins (HDL). To study alcohol's acute effects on plasma lipoproteins, we measured plasma lipoprotein concentrations and activities of postheparin plasma lipases in nine normolipemic males after ingestion of 40 g of ethanol (as whiskey). After alcohol there was no change in lipoprotein lipase activity but hepatic lipase was decreased to 67% of baseline at 6 hr. There were associated increases in HDL phospholipids (12 mg/dl) and cholesterol (10 mg/dl) resulting in prominence of larger, lipid-enriched HDL particles. Changes were most pronounced in the HDL3 and HDL2a subclasses. Very low density lipoprotein (VLDL) phospholipids and cholesterol were also increased by 13 and 9 mg/dl, respectively, with no significant change in triglycerides. Changes in lipoproteins and lipase were largely reversed 10 hr after alcohol intake. The transient increases in VLDL and HDL lipids after alcohol may result in part from acute inhibition of hepatic lipase activity. The results suggest a role of hepatic lipase in the catabolism of phospholipids of VLDL and possibly HDL.     

Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan-bound lipoprotein lipase

Apolipoprotein A5 (APOA5) is associated with differences in triglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasma triglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In human APOA5 transgenic mice (hAPOA5tr), catabolism of chylomicrons and very low density lipoprotein (VLDL) was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL). Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by cross-breeding a human LPL transgene with the apoa5 knock-out and the hAPOA5tr to an lpl-deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5-deficient mice; however, overexpression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr high density lipoprotein, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL-mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line. A direct interaction between LPL and apoAV was found by ligand blotting. It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycan-bound LPL for lipolysis.     

The effects of oral agent or insulin treatments on the plasma lipoproteins and the plasma lipoprotein lipase activator in diabetic patients

The structure and the metabolism of plasma lipoproteins are altered in diabetes mellitus. Insulin or oral agent treatments affect the lipoprotein metabolism in addition to improving hyperglycemia. However, it is not clear whether the alterations seen in lipoproteins during treatment are related to the degree of diabetic control or to the mode of diabetic treatment. The effects of insulin or oral agent treatments on the plasma lipoproteins and lipoprotein lipase activator were compared in a strictly defined non-obese, non-insulin dependent diabetic patient. Both treatment groups had similar plasma triglyceride, total cholesterol, low and high density lipoprotein cholesterol, and lipoprotein lipase activator levels. Lipoprotein lipase activator contents of the very low density lipoproteins correlated positively with their triglyceride (r = 0.803 in insulin, r = 0.828 in oral agent treated patients) and protein (r = 0.713 in insulin, r = 0.862 in oral agent treated patients) contents. The findings of this study indicated that plasma lipid levels, very low density lipoprotein compositions, and lipoprotein lipase activator contents were not significantly different in non-obese, non-insulin dependent diabetic patients treated with either oral hypoglycemic agents or insulin.     

Human plasma lipoproteins as accelerators of prothrombin activation.

The activation rate of bovine prothrombin by Factor Xa and Ca2+ has long been known to be greatly enhanced by addition of phospholipid. Upon substitution of human plasma lipoproteins for phospholipid (cephalin) in this activation system, only very low density lipoprotein enhances prothrombin activation. Low density lipoprotein and high density lipoprotein have no stimulatory effect on prothrombin activation. On the other hand, the sonicated lipid extracts from very low, low, and high density lipoproteins all can substitute for phospholipid in potentiating prothrombin activation. The efficiency of each lipid extract, in this regard, depends upon its source of extraction, and is greatest for the lipid extract of very low density lipoprotein.     

Analysis and lipoprotein lipase activation capacity of plasma lipoproteins isolated from atherosclerosis-susceptible White Carneau pigeon and atherosclerosis-resistant Show Racer pigeon

The lipoprotein composition and apoprotein composition of the major lipoprotein fraction (high density lipoprotein) were compared in White Carneau and Show Racer plasma. The capacity of the plasma and lipoproteins to activate the triacylglycerol hydrolyzing activity of lipoprotein lipase in vitro was compared in the two strains of birds and found to be identical in each case. It appears unlikely that differences in lipoprotein composition or tissue lipoprotein lipase activity will be reflected in the flux rates of lipoproteins in the two strains which have different susceptibilities to atherosclerosis.     

Glucose tolerance, plasma lipoproteins and tissue lipoprotein lipase activities in body builders

Oral glucose tolerance, insulin binding to erythrocyte receptors, serum lipids, and lipoproteins, and lipoprotein lipase activities of adipose tissue and skeletal muscle were measured in nine body builders (relative body weight (RBW) 118 +/- 4%), eight weight-matched (RBW 120 +/- 5%) and seven normal-weight controls (RBW 111 +/- 3%). The body builders had 50% higher relative muscle mass of body weight (% muscle) and 50% smaller relative body fat content (% fat) than the two other groups (P less than 0.005). Maximal aerobic power was comparable in the three groups. In the oral glucose tolerance test (OGTT), blood glucose levels, and plasma insulin levels were lower (P less than 0.05) in the body builders than in weight-matched controls. Insulin binding to erythrocytes was similar in each group. On the basis of multiple linear regression analysis, 87% of the variation in plasma insulin response could be explained by body composition (% muscle and % fat) and VO2max. Plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) triglyceride concentrations were significantly lower in the body builders than in weight-matched controls. In comparison with the normal-weight group, the body builders had a lower total cholesterol level. High density lipoprotein (HDL) cholesterol, its subfractions (HDL2 and HDL3 cholesterol) and lipoprotein lipase (LPL) activities of adipose tissue and skeletal muscle were comparable in all three groups. Partial correlation analysis showed a positive relationship between plasma total triglyceride, total cholesterol and LDL cholesterol on the other hand and the % fat on the other.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations in plasma lipoproteins and heparin-releasable lipase activities in mice bearing the GRSL ascites tumor

The lipoproteins in GR mice bearing the transplanted GRSL ascites tumor were characterized by density gradient ultracentrifugation and SDS-polyacrylamide gel electrophoresis. In control mice the major proportion of the lipoproteins was found in the HDL density range, but on days 4 and 5 following tumor transplantation a gradual shift into the LDL density range was observed. At the same time the apolipoprotein E content increased at the expense of apolipoprotein A-I. VLDL became moderately elevated. On days 6 and 7 all lipoproteins except VLDL reached extremely low values. The C-apolipoproteins showed a remarkable shift in their relative proportions. Plasma lecithin:cholesterol acyltransferase activity showed no significant alteration in the course of tumor growth, but the triacylglycerol lipases in postheparin plasma were strongly decreased. Lipoprotein lipase had already started to decline on day 2 following tumor transplantation. However, when assayed in the presence of heat-inactivated control plasma, a decrease was not observed before day 5. This is suggestive of a depletion of a plasma cofactor preceding the final disappearance of the enzyme itself, and is compatible with the changing apolipoprotein C pattern. Hepatic lipase showed a 50% reduction between days 3 and 4. The lipoprotein alterations in tumor-bearing mice are explained as a direct consequence of the decreased lipase activities.     

Association of lysolecithin acyltransferase with the high density lipoproteins and its activation by the low density lipoproteins in normal human plasma.

The lysolecithin acyltransferase of human plasma is shown to be associated with the high-density lipoprotein fraction. Although the low density lipoproteins do not have intrinsic enzyme activity, their presence activated the enzyme 3--7-fold. This activation is not affected by heat-treatment of the low density lipoproteins, but is abolished by the addition of heparin.     

Changes in plasma lipoproteins and tissue lipoprotein lipase and salt-resistant lipase activities during spawning in the rainbow trout (Salmo gairdnerii R.)

1. Lipoprotein lipase and salt-resistant lipase activities increased in the ovaries but decreased in the adipose tissue of female trout in the months leading up to spawning. 2. The activity of the plasma cholesterol esterifying enzyme increased significantly immediately prior to spawning. 3. Plasma lipoprotein concentrations decreased during the approach to spawning. 4. These studies suggest that the developing ovaries in the trout receive their nutrients by lipolysis of plasma lipoproteins as well as by vitellogenin uptake; differentiation of the roles of the lipid stores in different tissues is proposed.     

Properties of plasma low density lipoproteins in patients with hypertriglyceridemia and ischemic heart disease

It has been shown that low-density plasma lipoproteins in patients with ischemic heart disease and hypertriglyceridemia are heavier in density, smaller in size, more negatively charged and more inclined to peroxide modification and aggregation than in healthy persons. The protein in the composition of such lipoproteins deviates towards the water phase, which may result in the masking of the domen, recognized by the BE-receptor and may lead to hyperlipidemia of a retaining character.     

Interaction of insecticides with human plasma lipoproteins

The binding of chlorinated hydrocarbon, carbamate and organophosphate insecticides to human low density plasma lipoproteins (LDL) and high density plasma lipoproteins (HDL) was studied at pH 7.0 and 16°C and 26°C by equilibrium dialysis, difference spectra and fluorescence. The results suggest interaction to be a partitioning rather than a stoichiometric binding process. Distribution is related to lipid content and composition of the lipoproteins. The K-values vary from 3 × 10⁵ M^?1 for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) to less than 10 M^?1 for nicotine and aldicarb, and ΔG_tr° is in the range of 7400 cal for DDT to less than 1000 cal for aldicarb and nicotine. The K and ΔG_tr° are inversely related to the water solubility of the insecticides. A significant role of plasma lipoproteins in the transport of slightly water soluble insecticides is suggested.     

Characterization of equine plasma lipoproteins after separation by density gradient

1. Plasma lipoproteins from six thoroughbred horses were separated by density gradient ultracentrifugation. For each sample, lipoprotein bands were visualized by means of a prestained plasma control and characterized by electrophoretic, chemical and morphological analysis. 2. Very low density lipoproteins (VLDL) were isolated at d less than 1.018 g/ml. 3. Two clearly resolved bands were detected in the low density lipoprotein fraction (LDL). The density limits were evaluated as follows: LDL1(1.028 less than d less than 1.045 g/ml) and LDL2(1.045 less than d less than 1.070 g/ml). Marked differences were observed in the chemical composition and particle size of LDL1 and LDL2 fractions. 4. High density lipoprotein fraction (HDL) was usually isolated as a single band, distributed over the range 1.075 less than d less than 1.180 g/ml. However, chemical composition and particle size revealed heterogeneity in HDL subfractions. 5. The density limit of LDL and HDL bands varied in each animal, indicating differences in equine lipoprotein distribution.     

The interaction of human plasma glycoaminoglycans with plasma lipoproteins.

Modifications of existing methods have allowed for the isolation and purification of various species of plasma glycosaminoglycans on the basis of their sulfate content and molecular size. All of the preparations precipitated human plasma low density lipoproteins (LDL); maximal precipitation occurred with amounts of glycans corresponding to 50 mug of hexuronate and 12 mg of LDL. The interaction of glycans with pyrene-labeled lipoproteins was also studied, measuring variations of the fluorescence emitted by the monomer (M) and excimer (E) species of the bound pyrene. The ratio IE/IM is proportional to c/eta, where c is the microscopic concentration of the pyrene confined to the hydrocarbon region of the lipoprotein and eta is the microviscosity of that region. To 0.12 mg of pyrene-labeled LDL, very low density lipoproteins (VLDL) or high density lipoproteins (HDL) were added increasing amounts of the various glycan preparations. The sulfate-rich species decreased the IE/IM ratio of LDL and HDL but not that of VLDL. This finding suggests that the glycan caused a change in lipoprotein conformation associated with either an increased volume or increased microscopic viscosity of the hydrocarbon region. The modification of LDL conformation could be prevented by proteolytic treatment of the sulfate-rich species or by addition to the system of suitable amounts of sulfate-poor species or of chrondroitin-4-sulfate, but could not be prevented by increased ionic concentration. These results suggest that the two main species of plasma glycans are important in maintaining adequate rheological properties of plasma lipoproteins.     

Modifications of enzyme activities in rat liver plasma membrane after carbon tetrachloride poisoning

Adenylate Cyclase activity is increased in the liver of animals treated with CCl4 (250 ul/100g body wt.) after 30 min. The maximum increase is observed 2 hours after administration of the hepatotoxin. Whereas, 3',5'-nucleotidephosphodiesterase decreases significantly throughout all the experiments. Our results present evidence that there is relationship between Adenylate Cyclase and Phosphodiesterase activity and suggest that intracellular calcium ion may mediate a regulation of the synthesis and degradation of cyclic nucleotides. It is difficult to determine the exact role Ca2+ plays in regulating these two opposing reactions. Thus, in the near future the work in this laboratory will be to define carefully the effects of the CCl4 on ions on these two systems.     

Change in rabbit plasma lipoprotein lipase activity after cephalic irradiation]

Modifications of the post-heparin lipoprotein lipasic activity in the plasma are studied after cephalic irradiation in the rabbit. Results indicate a 2/3 decrease of the enzymatic activity which is reduced to zero in half of the animals 16 hours after a 800 R irradiation.