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PubMed1989

Regional adiposity patterns in relation to lipids, lipoprotein cholesterol, and lipoprotein subfraction mass in men.

Anatomical adipose tissue distribution patterns are reported to relate to plasma lipids and risk of cardiovascular disease. Waist to hip girth ratios (WHR) and subscapular 10 triceps skinfold thickness ratios (STR) were compared with percent body fat and body mass index values as correlates of plasma lipids and lipoprotein cholesterol and serum lipoprotein subfraction mass by analytic ultracentrifugation in 81 sedentary middle-aged men in a typical range of adiposity. WHR was significantly and positively correlated with plasma concentrations of triglycerides, cholesterol, and low and very low density lipoprotein (LDL and VLDL) cholesterol and inversely correlated with high density lipoprotein (HDL) cholesterol. STR followed these trends, though less strongly, in relation to plasma triglycerides, VLDL cholesterol, and HDL cholesterol. Pronounced differences were found between regional adiposity patterns in their relationships to lipoprotein subfractions, as determined by analytic ultracentrifugation. WHR was negatively correlated with HDL2 (flotation rate F(1.2) 3.5-9), positively with small LDL (S.f 0-7), intermediate density lipoprotein (S.f 12-20), and VLDL (S.f 20-400), while STR correlated with larger LDL (S.f 7-12) and larger VLDL (S.f 60-400). Overall adiposity was not significantly associated with plasma lipoprotein levels after adjusting for regional adiposity patterns. Plasma sex hormone-binding globulin and percent free testosterone were associated with regional adiposity, but did not account for the correlations between WHR and lipoproteins. WHR and STR are measures of fat distribution that correlate with plasma lipoprotein profiles consistent with cardiovascular disease risk and have different relationships to lipoprotein mass subfractions.

Adipose Tissue↗
PubMed1987

Stimulation of cholesteryl ester synthesis in human monocyte-derived macrophages by low-density lipoproteins from type 1 (insulin-dependent) diabetic patients: the influence of non-enzymatic glycosylation of low-density lipoproteins.

Diabetes mellitus is an independent risk factor in the development of atherosclerosis. In this study we aimed to demonstrate whether there is an abnormal interaction between low-density lipoproteins from diabetic patients and human macrophages. We measured cholesteryl ester synthesis and cholesteryl ester accumulation in human monocyte-derived macrophages (obtained from non-diabetic donors) incubated with low density lipoproteins from Type 1 (insulin-dependent) diabetic patients in good or fair glycaemic control. Low density lipoproteins from the diabetic patients stimulated more cholesteryl ester synthesis than low density lipoproteins from non-diabetic control subjects (7.19 +/- 1.19 vs 6.11 +/- 0.94 nmol/mg cell protein/20 h, mean +/- SEM, p less than 0.05). The stimulation of cholesteryl ester synthesis by low density lipoproteins isolated from diabetic patients was paralleled by a significant increase in intracellular cholesteryl ester accumulation (p less than 0.02). There were no significant differences in the lipid composition of low density lipoproteins between the diabetic and control groups. Non-enzymatic glycosylation of low density lipoproteins was higher in the diabetic group (p less than 0.01) and correlated significantly with cholesteryl ester synthesis (r = 0.58). Similarly, low-density lipoproteins obtained from non-diabetic subjects and glycosylated in vitro stimulated more cholesteryl ester synthesis in macrophages than control low density lipoproteins. The increase in cholesteryl ester synthesis and accumulation by cells exposed to low density lipoproteins from diabetic patients seems to be mediated by an increased uptake of these lipoproteins by macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Very fast ultracentrifugation of serum lipoproteins: influence on lipoprotein separation and composition.

A very short run time and small sample volumes in the separation of lipoproteins by preparative ultracentrifugation are needed for several investigations. Recently, a very fast sequential separation method was described that needs only 100 min for one run in a centrifugal field of 625,000 x g. We studied the influence of centrifugal fields of this dimension on lipoprotein separation and lipoprotein particle integrity using a Beckman Optima TLX ultracentrifuge with a TLA-120.2 rotor. Rotor speed (120/90/60/30.10(3) rev./min) and run time (100 min/3 h/6.7 h/27 h) were selected in such a way that the product of centrifugal field and run time remained constant. The first conditions correspond to the very fast ultracentrifugation (VFU) procedure with a centrifugal field of 625,000 x g. Thirty different plasma samples covering a wide range of lipid and protein concentrations were separated in the course of two centrifugal runs at densities of 1.006 and 1.063 kg/l which yielded very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and the subnatant of low-density lipoproteins, including high-density lipoproteins (HDL) and concomitant sedimented plasma proteins. The major lipid components of the lipoproteins, triacylglycerols, free and esterified cholesterol, phospholipids and the apolipoproteins B and A-I, were estimated considering the masses of the tube contents after a slicing procedure. Measurements of lipids and proteins showed a very good recovery of better than 94% and 91%, respectively, and precision-within-series (coefficient of variation) of better than 4.2% and 6.5%, respectively. The effects of the rotor speed on the lipoprotein structure appeared to be weak. With increasing rotor speed, VLDL and LDL lipid constituents principally tended to decrease, whereas they increased in the subnatant of the LDL-run. The mean lipoprotein mass composition, considering the mass percentage of each measured particle constituent, did not show significant alterations. Total protein decreased in VLDL and in LDL and increased in the subnatant of the LDL-run. As checked by an enzyme-linked immunosorbent assay (ELISA) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), the protein effects were due to nearly complete disappearance of contaminating plasma proteins, especially albumin as the major contamination of VLDL and LDL. The apolipoproteins (apo) B-100, A-I, E and C-I to C-III remained nearly unaffected. The main advantages of VFU were the very short run time (cumulative flotation time is 3.4 h) and the elemination of albumin without repeated runs. The procedure was suitable for the assessment of lipid and protein constituents in lipoproteins from very small plasma samples (500 microliters).

Adult↗
PubMed1992

Lipoprotein assembly. Apolipoprotein B size determines lipoprotein core circumference.

Apolipoprotein B (apoB) is an essential structural protein for the two triglyceride-rich lipoproteins synthesized by humans: chylomicrons and very low density lipoproteins. Although much is known about the role of apoB in clearance of lipoproteins from the circulation, relatively little is known about its role in the assembly of nascent lipoproteins. Therefore, we have investigated the relationship between the length of various N-terminal apoB fragments and the characteristics of the lipoproteins with which these fragments were associated. After the addition of puromycin, HepG2 cells secreted a discrete series of C-terminally truncated apoB fragments on lipoprotein particles including apoB25, apoB29, apoB31, apoB33, apoB36, apoB38, apoB42, apoB45, apoB49, apoB51, apoB55, apoB70, and apoB80. Also, using plasmids encoding apoB26, apoB33, apoB37, apoB42, and apoB48, C-terminally truncated apoB fragments were expressed and secreted after transient transfection of HepG2 cells. Lipoproteins bearing the metabolically labeled apoB fragments were isolated from the cell culture media and characterized in terms of size, density, flotation coefficient, and composition. Lipoprotein radii, calculated from their flotation coefficients and buoyant densities, were used to derive the circumference of the non-polar core of each lipoprotein species. When plotted as a function of apoB size, core circumference defined a straight line of near-zero intercept. The slope of this line was approximately 1 A of core circumference/1 kDa of apoB molecular mass. A model for the mechanism of lipoprotein assembly in HepG2 cells, consistent with the concept that apoB size determines lipoprotein core circumference, is proposed.

Apolipoproteins B↗
PubMed1997

Metabolic factors clustering, lipoprotein cholesterol, apolipoprotein B, lipoprotein (a) and apolipoprotein E phenotypes in premature coronary artery disease in French Canadians.

Plasma lipoprotein cholesterol abnormalities, diabetes, hypertension and smoking have all been identified as independent predictors of cardiovascular events. Clustering of multiple risk factors suggests a common metabolic link among high blood pressure, insulin resistance, plasma lipoprotein abnormalities and obesity. New guidelines for the management of dyslipidemias target patients with established coronary artery disease (CAD), and high risk patients with multiple risk factors and severe genetic lipoprotein disorders, such as familial hypercholesterolemia. To determine the prevalence of lipoprotein, apolipoprotein and metabolic disorders in premature CAD, 243 men and 61 women with premature CAD (occurring before age 60 years) and 203 age- and sex-matched controls (152 men, 61 women) were studied. After correcting for beta-blocker use (40% of men and 54% of women), hypertension and diabetes were seen more frequently in CAD patients than in controls. In men and women, cholesterol, triglycerides, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein (a) were significantly higher, and high density lipoprotein (HDL) cholesterol was lower, in CAD patients than in controls. By stratifying patients according to LDL cholesterol: HDL cholesterol ratio (5 or less, or greater than 5) and by triglyceride levels (less than 2.3 mmol/L, or 2.3 mmol/L or greater), significantly more men and women with CAD were found to have an elevated LDL cholesterol:HDL cholesterol ratio and elevated triglycerides (13.8% versus 1.9%, men and women combined, CAD versus controls, P < 0.0001). A metabolic factor index was devised, assigning a score of 1 each for presence of hypertension, lipoprotein abnormalities, diabetes or fasting blood glucose above 7.0 mmol/L, and a body mass index of 27 or greater. The prevalence of a metabolic factor index of 3 or more was 29.2% in CAD men versus 6.7% in controls (P < 0.0001) and 38.3% in CAD women versus 11.7% in controls (P < 0.01). Familial hypercholesterolemia was seen in fewer than 5% of patients with premature CAD and type III dyslipoproteinemia in one of 343 CAD patients. The distribution of apolipoprotein E phenotypes was the same in CAD patients and controls. Multivariate analysis revealed that in men, HDL cholesterol, lipoprotein (a) levels and smoking were the best predictors of risk. In men, plasma levels of LDL cholesterol, triglycerides or body mass index did not enter the model at the P < 0.05 level. In women, low HDL cholesterol, lipoprotein (a), the presence of diabetes, smoking and apolipoprotein B levels were all predictors of risk (P < 0.05). However, the clustering of risk factors may be the best predictor of risk. In this selected population, HDL and lipoprotein (a) are the best metabolic markers of premature CAD; metabolic factor clustering is common in patients with premature CAD.

Adult↗
PubMed1986

Characterization of a monoclonal antibody that binds equally to all apolipoprotein and lipoprotein forms of human plasma apolipoprotein B. II. Isolation of apolipoprotein B-containing lipoproteins from human plasma.

Monoclonal antibody ('Pan B' antibody) that binds equally to all major forms of human plasma apolipoprotein B was used in an immunoaffinity chromatography procedure to isolate apolipoprotein B-containing lipoproteins from hyperlipidemic human plasma. These lipoproteins were compared with lipoproteins in native plasma, with lipoproteins isolated by polyclonal antibodies and with lipoproteins isolated by the conventional ultracentrifugational method. Judged by the apolipoprotein and lipid composition, lipoproteins isolated with 'Pan B' antibody were virtually identical to those isolated by ultracentrifugation or polyclonal antibodies. Lipoproteins isolated by 'Pan B' antibody were comparable in size and shape to the lipoproteins in native plasma and to the lipoproteins isolated by polyclonal antibodies or ultracentrifugation. The immunoaffinity column with monoclonal 'Pan B' antibody retained all apolipoprotein B-containing lipoproteins and showed significantly higher capacity than polyclonal immunoaffinity column. The column with the highest capacity allowed the isolation from whole plasma of 0.144 mg of apolipoprotein B per ml of gel in less than 2 h.

Animals↗
PubMed1980

Transfer of cholesterol esters between human high density lipoproteins and triglyceride-rich lipoproteins controlled by a plasma protein factor.

A protein factor from the d greater than 1.25 g/ml plasma fraction controls the transfer of cholesterol esters between high density lipoproteins and very low density lipoproteins. This transfer is time-dependent, and follows saturation kinetics relative to the concentration ratio of acceptor to donor lipoproteins. Although the process is reversible, the transfer rates are faster from high density to very low density lipoproteins and result in a net increase of cholesterol esters in the very low density lipoproteins. Under the same conditions, there is also a net mass transfer of cholesterol esters from high density lipoproteins to chylomicrons. This constitutes the first demonstration of cholesterol ester mass transfer between isolated lipoproteins and contrasts with the equilibrium of cholesterol esters between HDL and LDL which we previously demonstrated [4]. The apparent maximum transfer rate of cholesterol esters from high density to very low density lipoproteins was calculated to be about 80 nmoles cholesterol esters/h/ml plasma, which is very similar to the initial rate of reaction of lecithin:cholesterol acyltransferase in plasma. It is concluded that cholesterol ester formation in high density lipoproteins and their transfer to triglyceride-rich lipoproteins may be closely coupled.

Adult↗
PubMed1988

Effect of lipoprotein lipase and hepatic triglyceride lipase activity on the distribution of apolipoprotein E among the plasma lipoproteins.

The independent roles of human lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) in determining the distribution of apolipoprotein E (apo E) among the plasma lipoproteins has been studied in vitro. In one series of three studies, postheparin plasma (10%) was incubated for 2 h with autologous plasma and the changes in the lipoprotein association of apo E after lipase exposure were determined after lipoprotein fractionation on 4% agarose columns. Specificity for LPL or HTGL was achieved by inhibition with goat anti-human HTGL or with 1 M NaCl, respectively. In another study, LPL and HTGL were partially purified from human postheparin plasma. The independent effects of these enzymes on the lipoprotein association of apo E were then examined after incubation of plasma in the absence or presence of one or both lipases. Data from both types of in vitro study showed that LPL-mediated triglyceride hydrolysis in the absence of HTGL activity was accompanied by a loss of apo E from triglyceride-rich lipoproteins, a gain or no change in the apo E-containing lipoproteins the size of intermediate density lipoproteins (IDL) and inconsistent changes in the apo E mass associated with high density lipoproteins (HDL). HTGL activity, on the other hand, in the absence of LPL, resulted in a redistribution of apo E from lipoproteins the size of IDL and a gain by those of HDL size. These studies thus support previous in vivo studies which pointed toward a specific role for HTGL in the processing of apo E containing IDL.

Apolipoproteins↗
PubMed1975

Lp(alpha) lipoprotein and pre-beta1-lipoprotein in relation to lipid levels in males.

Previous studies have shown that a slow-moving pre-beta-lipoprotein fraction, named the pre-beta1-lipoprotein, occurred significantly more frequently among subjects with coronary heart disease (CHD) than among healthy individuals. This lipoprotein is closely related to, and probably identical with, the Lp(a) lipoprotein. Immunological tests likewise showed that Lp(a) lipoprotein was significantly more common among patients with CHD than among controls. Mean cholesterol and triglyceride levels were higher in pre-beta1-lipoprotein positive than in pre-beta1-lipoprotein negative individuals. Lp(a+) individuals tended to have higher serum cholesterol values than did Lp(a-) persons but there was no difference in the mean triglyceride value. This apparent discrepancy seems to be due to the presence in occasional sera of lipoprotein fractions with pre-beta1-mobility, usually of a VLDL nature. These lipoproteins are not associated with the Lp(a) lipoprotein.

Antigens↗
PubMed2003

Compositional lipoprotein changes and low-density lipoprotein susceptibility to oxidation in chronic renal failure patients with heavy proteinuria.

BACKGROUND: There are limited data regarding qualitative lipoprotein abnormalities in undialysed uremic patients without proteinuria. In this report, we focused on lipoprotein changes observed in uremic patients with proteinuria as well as on the susceptibility of low-density lipoprotein (LDL) of these patients to oxidative modification in vitro. METHODS: 20 patients with chronic renal failure [serum creatinine >1.6 mg/dl (141.4 micromol/l)], but not yet on renal replacement therapy, and with heavy proteinuria (>2 g/24 h), and 18 age- and sex-matched healthy individuals participated in the study. In both patients and controls, venous blood was collected for determination of serum lipid and lipoprotein levels, lipoprotein subfraction profile and chemical composition, as well as the susceptibility of LDL subfractions to oxidation. RESULTS: Patients exhibited a more atherogenic lipid profile compared with the control population. Furthermore, the total very LDL + intermediate-density lipoprotein mass was increased in patients compared with controls, while this subfraction was triglyceride enriched in uremic patients. The total LDL concentration was significantly higher in patients compared with controls due mainly to an increase in the mass of all lipoprotein subfractions. It is noteworthy that the mass of small dense LDL was significantly elevated in patients compared with controls (135 +/- 12 vs. 115 +/- 11 mg/dl, p = 0.01), an increase which was more pronounced in hypertriglyceridemic patients. Furthermore, the subfraction high-density lipoprotein-2 mass was significantly lower in uremic patients compared with controls. Finally, no significant differences in the lag time, the rate of oxidation and the relative electrophoretic mobility values in each LDL subfraction between the two groups were observed. CONCLUSION: We conclude that uremic patients with heavy proteinuria exhibit compositional lipoprotein changes that are less marked than those observed in nonuremic patients with nephrotic syndrome. However, there is no evidence that circulating LDL isolated from these patients is more susceptible to oxidation in vitro than lipoprotein isolated from age- and gender-matched controls.

Adult↗
PubMed1993

Correlation between the ratio of serum low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with that of serum apolipoproteins B and A-I.

Phosphowolframate/magnesium chloride, a commonly used precipitation method for the determination of high-density lipoprotein cholesterol in human serum, yields a supernatant containing almost all of the lipoproteins apo A-I and apo A-II but no lipoprotein apo B. The correlation between high-density lipoprotein cholesterol and apo A-I was very high (r = 0.94), as well as that between the precipitation method and ultracentrifugal analysis (r > 0.95, P < 0.001). In contrast, detergent precipitation (for the determination of low-density lipoprotein cholesterol in human serum) produced sediments which contained the major proportion of apo B and only minor amounts of apo A-I and apo A-II. The precipitation method for low-density lipoprotein cholesterol showed very good agreement with ultracentrifugal analysis (r = 0.99). Yields of 80.2% were obtained for apo B with both methods. Results obtained using the precipitation methods showed excellent agreement with those obtained using the Friedewald formula (r > 0.99). Results were also very similar when hypertriglyceridemic serum samples were briefly centrifuged before analysis of cholesterol, high-density lipoprotein cholesterol and triglyceride values. The present study shows highly significant correlations between cholesterol/high-density lipoprotein cholesterol or low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and apo B/apo A-I ratios (P < 0.001). Apo B and apo A-I levels could be used in addition to low- and high-density lipoprotein cholesterol values when assessing the risk of cardiovascular disease, if the methods for determining serum apolipoproteins have been properly standardized.

Apolipoprotein A-I↗
PubMed1993

Down-regulation of mRNA for the low density lipoprotein receptor in transgenic mice containing the gene for human cholesteryl ester transfer protein. Mechanism to explain accumulation of lipoprotein B particles.

To evaluate the effects of cholesteryl ester transfer protein (CETP) on apoB-containing lipoproteins, we analyzed plasma lipoproteins from three different lines of human CETP transgenic mice, with plasma CETP concentration ranging from low (1.5 microgram/ml) to high levels (8.5 micrograms/ml). With increasing CETP concentration, very low density lipoprotein and low density lipoprotein (LDL) cholesteryl ester (CE) and apoB were progressively increased, and high density lipoprotein CE was decreased. To investigate the mechanism of accumulation of lipoproteins containing apoB (lipoprotein B), the abundance of hepatic LDL receptor mRNA was determined. LDL receptor mRNA was reduced as a result of CETP expression, with maximum repression to about 48% of the level of non-transgenic mice. Among the different lines of CETP transgenic mice there was an inverse relationship between plasma CETP concentration and hepatic LDL receptor mRNA abundance (r = -0.94, p < 0.01). CETP expression also led to increased cholesterol and cholesteryl ester content in liver and to decreased abundance of mRNAs encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase and 7-alpha-hydroxylase. Thus, CETP expression results in increased cholesteryl ester concentration in very low density lipoprotein and LDL, probably reflecting both CE transfer from high density lipoprotein and accumulation of lipoprotein B particles. The accumulation of lipoprotein B particles results from CETP-mediated down-regulation of liver LDL receptors, possibly due to enhanced return of cholesterol to the liver.

Animals↗
PubMed1986

Role of lipoproteins in growth of human adult arterial endothelial and smooth muscle cells in low lipoprotein-deficient serum.

Recently improved culture conditions for human adult arterial endothelial and smooth muscle cells from a wide variety of donors have been used to study the effects of lipoproteins on proliferation of both cell types in low serum culture medium. Optimal growth of endothelial and smooth muscle cells in an optimal nutrient medium (MCDB 107) containing epidermal growth factor, a partially purified fraction from bovine brain, and 1% (v/v) lipoprotein-deficient serum was dependent on either high- or low-density lipoprotein. High- and low-density lipoprotein stimulated cell growth by three- and five-fold, respectively, over a 6-day period. Optimal stimulation of both endothelial and smooth muscle cell growth occurred between 20 and 60 micrograms/ml of high- and low-density lipoproteins, respectively. No correlation between the activation of 3-hydroxyl-3-methylglutaryl coenzyme. A reductase activity and lipoprotein-stimulated cell proliferation was observed. Lipid-free total apolipoproteins or apolipoprotein C peptides from high-density lipoprotein were partially effective and together with oleic acid effectively replaced native high-density lipoprotein for the support of endothelial cell growth. In contrast, apolipoproteins or apolipoprotein C peptides from high-density lipoprotein alone or with oleic acid had no effect on smooth muscle cell proliferation. The results suggest a functional role of high- and low-density lipoproteins and apolipoproteins in the proliferation of human adult endothelial and smooth muscle cells.

Apolipoproteins↗
PubMed1997

The effect of growth hormone replacement therapy for up to 12 months on lipoprotein composition and lipoprotein(a) in growth hormone-deficient adults.

The effect of growth hormone replacement therapy in near physiological doses on lipoprotein composition and serum lipoprotein(a) concentrations was investigated in growth hormone-deficient subjects. A randomised, double-blind, placebo-controlled trial of recombinant growth hormone was undertaken for 6 months followed by an open extension for a further 6 months (0.125 IU/kg per week for the first 4 weeks of each 6 month period and thereafter 0.25 IU/kg per week). A total of 18 patients with isolated growth hormone deficiency or hypopituitarism were studied. Lipid concentrations were estimated in lipoprotein fractions and protein concentrations were measured in low density lipoprotein (LDL). Glucose and glycated haemoglobin in blood and insulin, cholesterol, triglyceride, apolipoproteins A-I and B and lipoprotein(a) concentrations were measured in serum. In the placebo-controlled phase fasting blood glucose concentrations increased with growth hormone treatment from 5.0 +/- 0.2 to 5.8 +/- 0.2 mmol/l (P = 0.02) (mean +/- S.E.M.), although no significant changes were seen in lipids or lipoproteins. In the group receiving active treatment total serum cholesterol decreased from 6.0 +/- 0.4 to 5.2 +/- 0.3 mmol/l (P = 0.002) after 6 months, due to reduced LDL cholesterol concentrations. Low density lipoprotein protein concentrations fell (0.8 +/- 0.1 versus 0.7 +/- 0.1 g/l) (P = 0.005), and LDL phospholipid levels decreased from 0.9 +/- 0.1 to 0.7 +/- 0.1 mmol/l (P = 0.007). Serum cholesterol and LDL composition reverted to pre-treatment values by 12 months. Fasting blood glucose remained above pre-treatment values (P = 0.036) and fasting insulin was significantly increased (P = 0.044). There was no effect of growth hormone therapy on serum triglyceride, apolipoprotein or lipoprotein(a) concentrations. In conclusion, growth hormone therapy with near physiological doses has no long term effects on serum lipoprotein(a) concentrations or lipoprotein composition.

Adult↗
PubMed1996

Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults. II. Effects on serum lipoproteins and lipoprotein and hepatic lipase activity.

Recombinant human growth hormone (GH) administered as daily subcutaneous (SC) injections has been shown to affect serum lipoproteins in GH-deficient subjects. However, the effects of continuous infusion of GH on serum lipoproteins have not been investigated in GH-deficient adults. The aim of the present study was to compare effects of daily injections and continuous infusion of GH on lipoprotein metabolism. Recombinant human GH (0.25 U/kg/wk) was administered to nine GH-deficient adult men during a period of 14 days in two different ways, ie, as a daily SC injection at 8:00 PM and as a continuous SC infusion, with 1 month of washout between the treatments. Blood samples and tests were performed in the morning after an overnight fast before the start of GH treatment (day 0) and on day 2 and day 14 of treatment. Abdominal SC adipose tissue lipoprotein lipase (LPL), postheparin plasma LPL, and hepatic lipase (HL) activity were measured 120 minutes after the intake of 100 g glucose. Adipose tissue LPL activity decreased and postheparin plasma HL activity increased after 14 days of GH treatment irrespective of the mode of GH administration, whereas GH treatment had no effect on postheparin plasma LPL activity. Serum triglyceride and very-low-density lipoprotein (VLDL) triglyceride concentrations increased during GH treatment. However, VLDL triglyceride concentrations increased to a greater degree during treatment with daily GH injections than during continuous infusion of GH. Serum apolipoprotein (apo) B and low-density lipoprotein (LDL) cholesterol concentrations decreased during treatment with daily GH injections, but were not significantly affected by continuous GH infusion. Thus, apo B and LDL cholesterol concentrations were lower after daily GH injections versus continuous GH infusion. Serum lipoprotein(a) [Lp(a)] and apo E concentrations increased during both modes of GH treatment. However, continuous infusion of GH resulted in a more marked increase in Lp(a) and apo E concentrations than daily GH injections. Minor effects were observed on serum apo A-I concentrations but high-density lipoprotein (HDL) cholesterol concentrations were not affected. In conclusion, GH treatment of GH-deficient men influenced adipose tissue LPL and postheparin plasma HL activity, as well as serum lipoprotein concentrations. Moreover, continuous GH infusion and daily GH injections differed with respect to the magnitude of effects on several lipoprotein fractions including VLDL triglycerides, LDL cholesterol, apo B, apo E, and Lp(a) concentrations.

Adult↗
PubMed1998

Hepatic apo E expression is required for remnant lipoprotein clearance in the absence of the low density lipoprotein receptor.

According to the secretion-capture model of remnant lipoprotein clearance, apo E secreted by hepatocytes into the space of Disse serves to enrich the remnants with a ligand for receptor-mediated lipoprotein endocytosis. Current evidence supports a two-receptor model of lipoprotein removal, in which apo E-containing remnants bind either the low density lipoprotein receptor (LDLR) or the LDLR-related protein (LRP). Recently, we demonstrated that reconstitution of apo E(-/-) mice with apo E(+/+) marrow results in normalization of plasma lipoprotein levels, indicating that hepatic expression of apo E is not required for remnant clearance and calling into question the relevance of the secretion-capture mechanism. To dissect the relative contributions of LDLR and LRP to the cellular catabolism of remnant lipoproteins by the hepatocyte, bone marrow transplantation (BMT) was used to reconstitute macrophage expression of apo E in mice that were null for expression of both apo E and the LDLR. Reconstitution of macrophage apo E in apo E(-/-)/LDLR(-/-) mice had no effect on serum lipid and lipoprotein concentrations, although it produced plasma apo E levels up to 16-fold higher than in C57BL/6 controls. Immunocytochemistry of hepatic sections revealed abundant staining for apo E in the space of Disse, but no evidence of receptor-mediated endocytosis of remnant lipoproteins. Transient expression of human LDLR in the livers of apo E(+/+)--> apo E(-/-)/LDLR(-/-) mice by adenoviral gene transfer resulted in normalization of serum lipid levels and in the clearance of apo E-containing lipoproteins from the space of Disse. We conclude that whereas the LDLR efficiently clears remnant lipoproteins irrespective of the site of origin of apo E, endocytosis by the chylomicron remnant receptor (LRP) is absolutely dependent on hepatic expression of apo E. These data demonstrate in vivo the physiologic relevance of the apo E secretion-capture mechanism in the liver.

Animals↗
PubMed1993

Absence of triglyceride accumulation in lipoprotein lipase-deficient human monocyte-macrophages incubated with human very low density lipoprotein.

Lipoprotein lipase, a lipolytic enzyme essential for normal hydrolysis of triglycerides in very low density lipoprotein (VLDL) and chylomicrons, is found in several cell types, including macrophages. The role of lipoprotein lipase in mediating the uptake of normal VLDL triglycerides into human cultured monocyte-derived macrophages was studied using macrophage cells from a functionally lipoprotein lipase-deficient patient and macrophages of cells from a normal subject. After incubation with VLDL, massive accumulation of phase refractile (lipid) inclusions were noted by phase contrast microscopy within the normal, but not within the lipoprotein lipase-deficient, macrophages. Chemical determinations of intracellular lipid confirmed massive triglyceride accumulation within normal macrophages, but not in lipoprotein lipase-deficient macrophages. VLDL-derived cholesterol did not accumulate in either cell. These results confirm an additional role of lipoprotein lipase, that of mediating triglyceride accumulation into macrophages from normal human VLDL. Human monocyte-macrophages genetically deficient in a functional lipoprotein lipase will be useful to determine the role of lipoprotein lipase in macrophage accumulation of lipid from other forms of triglyceride-carrying lipoproteins, including hypertriglyceridemic VLDL, beta-VLDL, and chylomicrons.

Adult↗
PubMed1990

Lipoproteins and acute phase response during acute infection. Interrelationships between C-reactive protein and serum amyloid-A protein and lipoproteins.

To study the interrelations between the changes of acute phase proteins and those of serum lipoproteins in acute infections we measured the concentrations of different lipoproteins, serum amyloid-A protein and C-reactive protein and activities of lipoprotein lipase and hepatic lipase during acute and convalescence phase and after complete recovery in 64 patients with infectious diseases (30 with viral infection and 34 with bacterial infection). The maximal decrements of both low density lipoprotein and high density lipoprotein cholesterol correlated significantly with the acute phase levels of C-reactive protein and serum amyloid-A protein. The acute phase concentration of very low density lipoprotein triglyceride correlated inversely to C-reactive protein level (r = -0.31, P less than 0.05) but not to serum amyloid-A protein level. Regression analysis showed that the concentration of C-reactive protein was a significant predictor of very low density lipoprotein triglyceride level in the acute phase of infection but not during convalescence. These results and the previous findings that C-reactive protein binds to low and very low density lipoproteins and that serum amyloid-A protein is associated with high density lipoprotein give credence to the view that C-reactive protein and serum amyloid-A protein interfere with the metabolism of serum lipoproteins during acute phase of infection.

Acute-Phase Reaction↗