Heparin Lipoprotein Research Articles

INSULIN RESISTANCE IS AN ALIMENTARY DEFICIENCY OF ENERGY SUBSTRATES (GLUCOSE) IN THE BIOLOGICAL REACTION OF EXOTROPHY AND APHYSIOLOGY COMPENSATION BY FATTY ACIDS VIA THE BIOLOGICAL REACTION OF ENDOTHROPHY

The deficiency of energy substrates in the biological function of trophology and biological reaction of exotrophy is formed by two factors. Excess of meat in the diet leads to high content of palmitic fatty acid (FA) in hepatocytes and formation of palmitic triglycerides (TG). Post heparin lipoprotein lipase slowly hydrolyzes palmitic TG in blood plasma lipoproteins and releases small amounts of FA. If dietary carbohydrate content is low, the biological function of exotrophy does not provide the substrate from which hepatocytes can rapidly produce oleic nonesterified FA de novo. Energy substrate deficiency activates the biological function of adaptation and the biological reaction of compensation. Under the effect of epinephrin NEFA deficiency is compensated via the biological reaction of endotrophy and lipolysis in omental visceral fat cells. In insulin resistance (IR) syndrome, the biological function of feeding is realized nonphysiologically while the biological reaction of adaptation is realized physiologically. An increase in NEFA blood content physiologically blocks glucose uptake in cells. Biological role of insulin consists in conversion of distant ocean-living carnivorous (fish-eating) ancestors of Homo sapiens with palmitic type of FA metabolism into herbivorous dry land-living species with oleic type metabolism of FA. The IR syndrome can be normalized. To this end a) the patient's will to activate the cognitive biological function (intellect) and b) comprehension of the fact that phylogenetically dry land-living Homo sapiens has developed as a herbivorous but not carnivorous species. Concerning death rate, cardiovascular pathologies are dominating in populations of many countries, while feeding function disorders prevail in frequency. These disorders form the pathophysiological basis for all metabolic pandemias: 1) atherosclerosis and atheromatosis, 2) essential arterial hypertension, 3) metabolic syndrome, 4) obesity, 5) insulin resistance syndrome, 6) nonalcoholic fatty liver disease, and 7) endogenous hyperuricemia. Persistent potential deficiency of energy for realization of all biological reactions and functions is the major metabolic disorders in diabetes mellitus. Insulin resistance is a pathology associated primarily with FA and secondarily with glucose.

Antidyslipidemic and Antioxidant Activities of Tinospora cordifolia Stem Extract in Alloxan Induced Diabetic Rats

The antidyslipidemic activities of Tinospora cordifolia (T. cordifolia): family Menispermaceae, Hindi name: Giloya; Gurch or Tinospora in english, extract have been studied in alloxan induced diabetic rats. In this model, oral administration of stem extract (500 mg/kg bw. p.o.) for 30 days resulted significant decreased in the levels of blood glucose, plasma lipids and reactivated post heparin lipoprotein lipase activity in alloxan induced diabetic rats. Furthermore, the stem extract (50–500 μg) when tested for its antioxidant activity, shown to inhibit the generation of super oxide anions and hydroxyl radicals, in both enzymic and non-enzymic systems in vitro. The results of the present study demonstrated antidyslipidemic and antioxidant activities of T. cordifolia which could help in prevention of diabetic-dyslipidemia and related complications.

Antidyslipidemic and Antioxidant Activities of Hibiscus rosa sinensis Root Extract in Alloxan Induced Diabetic Rats

The antidyslipidemic activity of Hibiscus rosa sinensis (Malvaceae) root extract has been studied in alloxan induced diabetic rats. In this model, oral administration of root extract (500mg/kg bw. p.o.) for 15days resulted in significant decreased in the levels of blood glucose, plasma lipids and reactivated post heparin lipoprotein lipase activity in alloxan induced diabetic rats. Furthermore, the root extract (50-500μg) when tested for its antioxidant activity, inhibited the generation of super oxide anions and hydroxyl radicals, in both enzymic and non enzymic systems in vitro. The results of the present study demonstrated antidyslipidemic and antioxidant activities in root extract of H. rosa sinensis which could be used in prevention of diabetic-dyslipidemia and related complications.

Capillary electrochromatography and quartz crystal microbalance, valuable techniques in the study of heparin–lipoprotein interactions

Atherosclerosis is initiated when lipoproteins bind to proteoglycans (PGs) in arterial walls. The binding is mediated by apolipoprotein apoB-100 and/or apoE, both of which have binding affinity toward heparin. We developed covalently bound heparin coatings for APTES-modified silica capillaries and SiO2 chips and carried out capillary electrochromatography (CEC) and quartz crystal microbalance (QCM) studies on the interactions of heparin with selected peptide fragments of apoB-100 and apoE and, for CEC, also with low- and high-density lipoproteins (LDL and HDL), the latter with and without apoE. The peptides are known to mediate interactions of HDL and LDL with arterial PGs. Interactions and affinities were expressed in CEC as retention factors and reduced mobilities and in continuous flow QCM techniques as affinity constants. Both techniques showed heparin interactions to be stronger with apoB-100 peptide than with apoE peptide fragment, and they confirmed that the sulfate groups in heparin play an especially important role in interactions with apoB-100 peptide fragments. In addition, CEC confirmed the importance of sulfate groups of heparin in interactions between heparin and LDL and between heparin and apoE-containing HDL. CEC and QCM acted as excellent platforms to mimic these biologically important interactions, with small sample and reagent consumption.

Ciprofibrate increases cholesteryl ester transfer protein gene expression and the indirect reverse cholesterol transport to the liver

BackgroundCETP is a plasma protein that modulates atherosclerosis risk through its HDL-cholesterol reducing action. The aim of this work was to examine the effect of the PPARα agonist, ciprofibrate, on the CETP gene expression, in the presence and absence of apolipoprotein (apo) CIII induced hypertriglyceridemia, and its impact on the HDL metabolism.ResultsMice expressing apo CIII and/or CETP and non-transgenic littermates (CIII, CIII/CETP, CETP, non-Tg) were treated with ciprofibrate during 3 weeks. Drug treatment reduced plasma triglycerides (30-43%) and non-esterified fatty acids (19-47%) levels. Cholesterol (chol) distribution in plasma lipoprotein responses to ciprofibrate treatment was dependent on the genotypes. Treated CIII expressing mice presented elevation in VLDL-chol and reduction in HDL-chol. Treated CETP expressing mice responded with reduction in LDL-chol whereas in non-Tg mice the LDL-chol increased. In addition, ciprofibrate increased plasma post heparin lipoprotein lipase activity (1.3-2.1 fold) in all groups but hepatic lipase activity decreased in treated CETP and non-Tg mice. Plasma CETP activity and liver CETP mRNA levels were significantly increased in treated CIII/CETP and CETP mice (30-100%). Kinetic studies with 3H-cholesteryl ether (CEt) labelled HDL showed a 50% reduction in the 3H-CEt found in the LDL fraction in ciprofibrate treated compared to non-treated CETP mice. This means that 3H-CEt transferred from HDL to LDL was more efficiently removed from the plasma in the fibrate treated mice. Accordingly, the amount of 3H-CEt recovered in the liver 6 hours after HDL injection was increased by 35%.ConclusionTogether these data showed that the PPARα agonist ciprofibrate stimulates CETP gene expression and changes the cholesterol flow through the reverse cholesterol transport, increasing plasma cholesterol removal through LDL.

Severe hypertriglyceridemia is related to episodes of epididymitis

Severe hypertriglyceridemia can lead to hepatospleomegaly, eruptive xanthomata, and dysfunction of several organ systems, including acute pancreatitis. In this study, we describe acute epidydimitis reoccuring in a case of Fredrickson type I hyperlipoproteinemia. We believe this to be the second published report and the first in a child with severe hypertriglyceridemia and acute epidydimitis. The etiology of the hypertriglyceridemia was confirmed by the measurement of the enzymatic activity of post—heparin lipoprotein lipase (LPL) (undetectable) and demonstration of compound heterozygosity with gene mutations at Gly188Glu and D250N.

HIV infection significantly reduces lipoprotein lipase which remains low after 6 months of antiretroviral therapy

Purpose of the study Fractional clearance rate of apolipoprotein B100-containing lipoproteins is reduced in HIV infection before and after antiretroviral (ARV) treatment [1]. We compared lipoprotein lipase (LPL) activity and gene expression in HIV-positive subjects before and 6 months after ARV with HIV-negative controls. Methods Fasting blood post heparin total and hepatic lipase activity,adiponectin, leptin, insulin, glucose, and lipid measurementswere made in 32 HIV-infected and 15 HIVnegative controls. LPL was estimated by subtractinghepatic lipase from total lipase. Adiponectin, LPL andhormone sensitive lipase (HSL) gene expression weremeasured from iliac crest subcutaneous fat biopsies.Patients were tested before, and 6 months after randomisation to AZT/3TC (n = 15) or TDF/FTC (n = 17) with EFV.Between-group comparison was by Mann-Whitney andpaired samples by the Wilcoxon signed rank tests. Summary of results There were no differences in gender, ethnicity, baseline BMI, regional fat distribution (whole body DEXA) and visceral (VAT) and subcutaneous fat (SAT) measured by abdominal CT scans between controls and patients. Trunk fat/BMI ratio, VAT and VAT:SAT ratio significantly increased after 6-month ARV therapy (p = 0.01). There were no differences between groups in serum NEFA,HOMA and leptin levels. Selected other results are shown in Table 1. Conclusion Post heparin lipoprotein lipase activity is reduced in HIV and does not return to control levels after 6 months of ARV therapy. AZT-containing regimens are associated with a greater increase in LPL, LPL gene expression and plasma adiponectin than TDF.

Cutaneous xanthomata associated with diabetes mellitus in a cat

ABSTRACTA 1,1/2 year‐old neutered male cat was presented with a non pruritic skin disease. Pale plaque‐like lesions were present on the face, head, axillae and ventral abdomen. Hypercholesterolaemia, hypertriglyceridaemia, hyperglycaemia and glycosuria were all present and histopathological examination confirmed that the skin lesions were xanthomata. A lipoprotein profile revealed an increase in chylomicrons, very low density lipoproteins and low density lipoproteins, and low post heparin lipoprotein lipase activity was present. A diagnosis of diabetes mellitus was made and following treatment with insulin and a change to a low fat, low carbohydrate diet the cat had normal values for blood lipids and glucose and the skin lesions had resolved within a month.

Activation of human post heparin lipoprotein lipase by apolipoprotein H (β 2-glycoprotein I)

Lipoprotein lipase (LPL) is the major enzyme involved in triglyceride hydrolysis of lymph chylomicrons and plasma very low density lipoproteins. LPL can be isolated from human post heparin plasma by heparin-Sepharose 4B affinity chromatography. In the present study the effects of apolipoproteins (apo) C-II, C-III, and H on the enzymic activity of LPL were investigated. ApoH is a recently described protein (β 2-glycoprotein I) constituent of triglyceride rich lipoproteins in human lymph and plasma. Human LPL was activated by apoC-II, and the apoC-II activation of LPL was inhibited by apoC-III. ApoH increased the enzymic activity of LPL in the presence of apoC-II by 45±17 percent. ApoC-III decreased the apoH + apoC-II enhanced activity of LPL by 77 percent. These results provide evidence for the concept that the enzymic activity of LPL in triglyceride metabolism is modulated by apoH. The relative proportion of apoH, apoC-II, and apoC-III in triglyceride rich lipoprotein particles may determine the ultimate rate of LPL catalyzed triglyceride hydrolysis.

Mechanism of heparin and serum lipoprotein interaction: Effects of calcium, phosphorylcholine, and a serum fraction

The mechanism of formation of an insoluble complex between heparin and rat serum lipoprotein has been studied. Optical density changes during the reaction, counting of the fatty acid labelled lipoproteins in the precipitates, and complexing of [14C]palmitate-labelled lipoprotein with heparin-CNBr-Sepharose were used to quantitatively determine the formation of insoluble complexes. The maximal heparin--lipoprotein complex formation requires 25--30 mM of Ca2+, but with micromolar amounts of phosphorylcholine, the reaction was saturated at only 10 mM of Ca2+. The effect of phosphorylcholine in promoting the reaction was lost when purified chylomicrons or very low density lipoproteins were used. The effect of phosphorylcholine in promoting the interaction between heparin and pure chylomicrons or very low density lipoproteins was regained when a crude serum protein factor of unwashed chylomicrons was added to the system, suggesting that rat serum contains a protein factor(s) which normally inhibits the heparin--lipoprotein interaction by raising the requirement of Ca2+. Phosphorylcholine counteracted the effect of this protein, thereby favouring the precipitation reaction in the presence of much lower concentration of Ca2+. The results have been discussed with special reference to the possibility of a relationship between mucopolysaccharides, Ca2+, lipoproteins, and arterial phospholipids in the pathogenesis of atherosclerosis.

The hypolipemic properties of 5β-cholanic acid in the mouse and rat

Dietary 5β-cholanic acid in the mouse caused a marked reduction of plasma cholesterol, an increase in rate of excretion of intraperitoneally administered 14C-labeled cholic and chenodeoxycholic acids and an increase in rate of excretion of orally administered 14C-labeled cholesterol. In this species it also caused a reduction in plasma triglycerides and an increase in liver size. Dietary 5β-cholanic acid did not greatly influence the rate of synthesis of cholesterol by liver homogenates of normally fed mice, but did cause a striking increase in this parameter in mice in which liver cholesterol synthesis had been suppressed by feeding cholesterol. In the rat 5β-cholanic acid caused a striking reduction in plasma triglycerides, but in sharp contrast to the effect observed in the mouse, a mild elevation of plasma cholesterol. In in vitro and in vivo experiments, in the presence and absence of depressed cholesterol synthesis by dietary cholesterol, 5β-cholanic acid caused a marked increase in rate of cholesterol synthesis by rat liver homogenates. Finally, in the rat, 5β-cholanic acid caused a sharp increase in plasma post heparin lipoprotein lipase activity.

Post heparin plasma lipoprotein lipase activity in thyroid disease.

ABSTRACT Plasma post heparin lipoprotein lipase activity (LLA) has been studied in patients with hyper- and hypothyroidism and in rabbits made thyrotoxic with thyroxine. The hypothyroid patients had high triglyceride and low LLA values as compared with a control group of healthy subjects. Statistically highly significant negative correlation was found between the triglycerides in fasting patients and the post heparin LLA, indicating a causal relationship, possibly with disturbance of chylomicron degradation due to low LLA in the arterial wall. However, relatively low LLA values were also demonstrated in hyperthyroid patients as well as in rabbits following treatment with thyroxine for 3 weeks. A stimulating effect of the thyroid hormones on the synthesis and degradation of lipoprotein lipase may be a possible explanation for these apparently contradictory findings.

Significance of adipose tissue lipoprotein lipase.

THE post-heparin clearing factor in plasma has the same properties as tissue lipoprotein lipase; this is explained by Korn1 by the fact that by the action of heparin lipoprotein lipase is released from the tissues in the blood stream. The greatest amount of lipoprotein lipase was found in adipose tissue2. A number of observations suggest indirectly the possible physiological significance of this enzyme in adipose tissue, particularly during the mobilization of fat from depots3–7. We have tried to elucidate the significance of adipose tissue lipoprotein lipase in rats by investigating the changes of its activity (a) after the administration of heparin and (b) during the mobilization and deposition of fat.

Studies of fat lipolysis by post-heparin human plasma lipoprotein lipase and by human pancreatic lipase.

Many studies indicate that unsaturated fats may lower serum cholesterol whereas saturated fats of animal origin usually increase it. The mechanism of these differing actions is unexplained, however. It has also been demonstrated that alimentary lipemia is cleared largely by an enzymatic lipolytic mechanism in which heparin is involved (heparin lipoprotein lipase). In this paper differences in hydrolysis of saturated and unsaturated fats by the heparin lipolytic factor are studied.

In vitro studies of human plasma lipolytic activity before and after oral fat intake.

The rate of in vitro lipolysis of added human low density lipoproteins was determined in 22 normal individuals using fasting and lipemic plasma. Unesterified fatty acid release was found in 16 subjects in all, in 10 in the fasting plasma and in 14 in the postlipemic plama. Lipolytic activity was greater in the lipemic sample in eight of the 16 individuals, in three it was unchanged before or after fat intake, and in five it was higher in the fasting sample. Addition of deoxycholate, which decreases heparin clearing factor and increases pancreatic lipase activity, inhibited lipolysis in most of the subjects and increased it in a few. Studies using beta-naphthol laurate, which in the presence of taurocholate is an excellent substrate for human pancreatic lipase but not for postheparin lipolytic activity, showed no hydrolysis in eight subjects, in six of whom lipolysis of the lipoproteins occurred. The results of the study suggest that increased plasma lipolytic activity is sometimes present after the ingestion of fat. They further indicate that endogenous heparin lipoprotein lipase is the major plasma enzyme involved in the splitting of neutral fat, but that a lipase similar to pancreatic lipase may be present less frequently, in small amounts, and may require added bile for activity. Submitted on February 20, 1957

Human endogenous plasma lipemia clearing and lipolytic activity after tricalcium phosphate adsorption.

Tricalcium phosphate gel removes all or the major portion of post-heparin clearing factor activity from plasma but does not decrease the activity of human pancreatic lipase. It is therefore a useful agent in identifying heparin lipoprotein lipase. Endogenous plasma lipolytic activity is completely or nearly completely removed after gel adsorption in almost all subjects in whom it is present, affording further evidence of its similarity to or identity with post-heparin factor. Plasma cholesterol ester and cholesterol esterase is also apparently decreased in the post-adsorptive sample.