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PubMed1986

Inhibition of human and rat lipoprotein lipase by high-density lipoprotein.

The hydrolysis in vitro of preactivated Intralipid (an artificial triacylglycerol-phospholipid emulsion) by rat adipose tissue lipoprotein lipase is inhibited by rat high-density lipoprotein (HDL). The aim of this work was to investigate whether human lipoprotein lipase was also inhibited, the mechanism of inhibition of the rat enzyme by HDL, and the role of the various individual apolipoproteins. Both human and rat lipoprotein lipase from post-heparin plasma are inhibited by HDL. This inhibition is considerably decreased if the HDL is first made 'apolipoprotein poor' by removal of some transferable apolipoproteins. In contrast, both native and apolipoprotein poor HDL inhibit the hydrolysis of Intralipid by rat hepatic lipase. Apolipoproteins C and E, either free in solution or attached to lipid vesicles, inhibit the hydrolysis of activated Intralipid by rat lipoprotein lipase to a maximum of 85% and 50%, respectively. Apolipoprotein A attached to vesicles gives little inhibition. HDL apolipoprotein and apolipoprotein C compete with the substrate for binding to lipoprotein lipase with apolipoprotein C having a higher affinity for the enzyme than HDL apolipoprotein. The inhibition of lipoprotein lipase by HDL can be explained by the association of the constituent apolipoproteins, in particular apolipoprotein C, with the enzyme so that there is less enzyme available to act on substrate.

Animals↗
PubMed1986

Analysis of plasma lipoproteins by ultracentrifugation in a new fixed angle rotor: evaluation of a phosphotungstic acid/MgCl2 precipitation and a quantitative lipoprotein electrophoresis assay.

A routine procedure for the ultracentrifugal analysis of human plasma lipoproteins by means of a fixed angle rotor was developed. It was applied as reference method for the evaluation of two widely used procedures of lipoprotein analysis, i.e. measurement of HDL-cholesterol after precipitation of the apolipoprotein B containing lipoproteins with a new phosphotungstic acid/MgCl2 reagent, and a quantitative lipoprotein electrophoresis system. A new statistical approach to the multivariate comparison of analytical methods, the linear structural relationship model, has been applied. The HDL-cholesterol levels measured after phosphotungstic acid/MgCl2 precipitation agreed well to those determined by ultracentrifugation, whereas electrophoretically quantified alpha-lipoprotein-cholesterol exceeded the ultracentrifugal HDL-cholesterol. The Friedewald formula obviously underestimated LDL-cholesterol due to an overestimation of VLDL-cholesterol, whereas the electrophoretically quantified pre-beta- and beta-lipoprotein-cholesterol levels fairly coincided with the respective ultracentrifugal measurements. The inter-assay reproducibility of the HDL-cholesterol determination after phosphotungstic acid/MgCl2 precipitation and subsequent LDL-cholesterol quantification according to Friedewald was statistically equivalent to that of ultracentrifugation, whereas the quantitative lipoprotein electrophoresis proved less precise.

Animals↗
PubMed1999

Alterations in low-density lipoprotein and high-density lipoprotein subclasses among Hispanic women with polycystic ovary syndrome: influence of insulin and genetic factors.

OBJECTIVE: To examine the influence of hyperandrogenism on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclass levels as well as lipoprotein (a) levels in hyperandrogenic women compared with a control group. DESIGN: Case-control study. SETTING: University-based outpatient clinic. PATIENT(S): Sixteen Hispanic women with polycystic ovary syndrome were compared with 21 controls matched for age, weight, and ethnicity. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fasting serum levels of testosterone, insulin, and lipoproteins. RESULT(S): Compared with controls, women with polycystic ovary syndrome had significantly lower levels of apolipoprotein A-I (95+/-28 mg/dL versus 144+/-42 mg/dL) and HDL2a (30.9%+/-4.4% versus 36.6%+/-5.4%) but significantly higher levels of HDL3c (5.1%+/-2.2% versus 2.4%+/-1.5%). There were no statistically significant differences in LDL subclasses between groups, but there was a high incidence (54%) of the atherogenic lipoprotein phenotype B in this Hispanic population. As a group, Hispanic women with the abnormal B phenotype had significantly higher levels of insulin, HDL, HDL2b, and triglycerides. CONCLUSION(S): Hyperandrogenemia may have an adverse effect on serum lipoproteins through effects on HDL subclasses. Hispanic women may have a higher incidence of the atherogenic lipoprotein phenotype B, which may increase their risk for atherosclerosis.

Adult↗
PubMed1998

Low-density lipoprotein modification occurring in human plasma possible mechanism of in vivo lipoprotein desialylation as a primary step of atherogenic modification.

We previously found in human blood a fraction of low-density lipoprotein (LDL) that is characterized by a reduced content of sialic acid. Desialylated LDL also has a low neutral carbohydrate level, decreased content of major lipids, small size, high density, increased electronegative charge and altered tertiary apolipoprotein B structure. Unlike native LDL, this fraction of desialylated (multiple-modified) LDL induces the accumulation of lipids in smooth muscle cells cultured from unaffected human aortic intima, i.e. it exhibits atherogenic properties. In this study, we attempted to elucidate the mechanism of desialylation and other changes in the multiple-modified LDL by investigating the possibility of LDL modification by different cells and the blood plasma. A 24-h incubation at 37 degrees C of lipoprotein with intact endotheliocytes, hepatocytes, macrophages and smooth muscle cells or cell homogenates did not cause alterations either in the physical properties or in the chemical composition of native LDL. On the other hand, a significant fall in the lipoprotein sialic acid level was observed already after a 1-h incubation of native LDL with an autologous plasma-derived serum. While LDL sialic acid level continuously decreased, LDL became capable of inducing the accumulation of total cholesterol in the smooth muscle cells cultured from unaffected human aortic intima after 3 h of incubation. Starting from the sixth hour of LDL incubation with serum, a steady decrease in the lipoprotein lipid content was observed as well as the related reduction of LDL size. Following 36 h of incubation, an increase in the negative charge of lipoprotein particles was also seen. Prolonged incubation of LDL with plasma-derived serum (48 and 72 h) leads to the loss of alpha-tocopherol by the LDL as well as to an increase in LDL susceptibility to copper oxidation and to accumulation of cholesterol covalently bound to apolipoprotein B, a marker of lipoperoxidation. Degradation of apolipoprotein B starts within the same period of time. Hence, desialylation of LDL particles represents one of the first or the primary act of modification which is, apparently, a sufficient prerequisite for the development of atherogenic properties. Subsequent modifications just enhance the atherogenic potential of LDL. The loss of sialic acid by LDL occurred at neutral pH and was not inhibited by the sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid. The [3H]sialic acid removed from LDL was not found in free form, but in the plasma fraction precipitated by trichloroacetic acid. These data along with the fact that cytidine-5'-triphosphate inhibited LDL desialylation suggest that enzymes close to sialyltransferases play a role in this process. Thus, this study demonstrated that the LDL modification processes imparting atherogenic properties to this lipoprotein can take place in human blood plasma. Multiple modification of LDL is a cascade of successive changes in the lipoprotein particle: desialylation, loss of lipids, reduction in particle size, increase of its electronegative charge and peroxidation of lipids.

Aorta↗
PubMed1994

Are lipoprotein profile and lipoprotein (a) levels altered in men with psoriasis?

BACKGROUND: Previous studies have demonstrated that patients with psoriasis may have an increased risk of a variety of noncutaneous diseases, including arterial and venous occlusive diseases. Changes in plasma lipid and lipoprotein composition in patients with psoriasis may be the reason for the increased risk of atherosclerosis in these patients. Lipoprotein (a) (Lp(a)) is a genetically determined lipoprotein associated with an increased prevalence of atherosclerotic and thrombotic cardiovascular diseases. OBJECTIVE: The aim of this prospective study was to determine the lipid profile and to define the significance of Lp(a) levels in men with psoriasis. The other purpose was to learn whether a correlation exists between psoriasis area and severity index score and serum Lp(a) or other lipids. METHODS: Serum Lp(a) levels were measured with a commercially available noncompetitive enzyme-linked immunosorbent assay in 32 men with psoriasis and in 13 healthy men. Total serum cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, apolipoprotein A-I and apolipoprotein B levels, and atherosclerotic risk factors other than hyperlipidemia were determined. Secondary hyperlipidemia from various diseases and drugs was ruled out in both groups. RESULTS: Serum Lp(a) levels were higher in men with psoriasis than in healthy male subjects, but the difference was not significant (p = 0.063). Serum fasting glucose levels were also found to be higher in the psoriasis group (p < 0.05). Higher serum Lp(a) and fasting glucose levels tended to occur in patients with extensive and severe skin involvement. No statistical differences were observed in the total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, apolipoprotein A-I, and apolipoprotein B levels between the two groups (p > 0.05). CONCLUSION: Our results suggest that the increased Lp(a) level might be a factor involved in occlusive vascular disorders in patients with psoriasis and that patients with extensive and severe skin involvement are more predisposed to relatively high Lp(a) levels.

Adolescent↗
PubMed1999

Antioxidant protection of lipoproteins containing estrogens: in vitro evidence for low- and high-density lipoproteins as estrogen carriers.

Some recent studies have reported that low-density lipoprotein (LDL) isolated from estrogen-treated postmenopausal women exhibited increased oxidation resistance ex vivo. However, the underlying mechanisms responsible for this effect are not clear. We explored the possibility that lipophilic derivatives of 17beta-estradiol (E(2)) could be incorporated into LDL and high-density lipoprotein (HDL) particles inhibiting lipoprotein oxidation. Introduction of small amounts of esterified E(2) into lipoproteins by means of incubation of free E(2) and E(2) 17-stearate in plasma did not result in any antioxidant effect. Using an artificial transfer system (Celite dispersion), larger amounts of E(2) esters could be incorporated into lipoproteins. Concentrations ranging between 0.27 and 1.38 molecules/LDL particle for E(2) 17-stearate and between 0.36 and 1.93 molecules/LDL particle for E(2) 17-oleate resulted in increased Cu(2+)-induced oxidation resistance of LDL as indicated by statistically significant lag time prolongations. Significant prolongations of lag times were also observed for HDL following incorporation of E(2) esters using Celite as transfer system. Our results suggest that free E(2) can be esterified and incorporated into lipoproteins during incubation in plasma. However, incorporation of supraphysiologic concentrations of E(2) esters into lipoproteins by means of the artificial transfer system was required in order to reduce their oxidation susceptibility.

Adult↗
PubMed1982

High-affinity uptake and degradation of apolipoprotein E free high-density lipoprotein and low-density lipoprotein in cultured porcine hepatocytes.

Isolated pig liver membranes contain a specific "lipoprotein binding site" that recognizes low-density lipoproteins (LDL) and apolipoprotein E (apoE) free high-density lipoprotein (HDL) [Bachorik, P. S., Kwiterovich, P. O., & Cooke, J. (1978) Biochemistry 17, 5287-5299]. We report here that a similar site exists in cultured porcine hepatocytes and that it mediates the uptake and degradation of apoE-free HDL. The binding of 125I-labeled HDL and 125I-labeled LDL (125I-HDL and 125I-LDL, respectively) at 4 degrees C and the uptake and degradation of the lipoproteins at 37 degrees C were time dependent and saturable and were not inhibited by unrelated proteins. Chloroquine (6 x 10(-5)M) inhibited the degradation of 125I-HDL by 76% and of 125I-LDL by greater than 99%; leupeptin inhibited the degradation of both lipoproteins by about 25%. 125I-HDL binding (4 degrees C), uptake, and degradation (37 degrees C) were inhibited by LDL, methyl-LDL, and methyl-HDL about as well as by unlabeled HDL but were unaltered in Pronase-treated cells or in cells that were cultured for 24 h in either lipoprotein-free medium containing HDL or LDL (200 micrograms/mL). In contrast, these conditions affected the uptake and degradation of 125I-LDL disproportionately. HDL and methyl-LDL inhibited 125I-LDL uptake by 50% or more but had little effect on degradation. 125I-LDL binding was reduced by 12% and degradation by 57% in Pronase-treated cells. Preincubation of the cells with LDL (200 micrograms/mL) reduced uptake by 35% and degradation by 68%. Similar preincubation with HDL (200 micrograms/mL) increased 125I-LDL degradation by 60% but did not affect 125I-LDL uptake. The findings indicated the presence in porcine hepatocytes of at least two distinct sites for lipoproteins. One site resembled the LDL receptor and mediated 125I-LDL degradation. A second, Pronase-insensitive site recognized both HDL and LDL. This site mediated almost all of the degradation of 125I-HDL but little if any degradation of 125I-LDL.

Animals↗
PubMed1981

Action of low-density lipoprotein and compactin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, on the synthesis of dolichol-linked oligosaccharides and low-density-lipoprotein receptor in human skin fibroblasts.

To explore whether there is an inter-relationship between the rate of low-density (LD) lipoprotein binding to its receptor and the formation of dolichol-linked oligosaccharides, experiments were performed with human fibroblasts where the synthesis of lipoprotein receptor and dolichyl saccharides was under control of LD lipoprotein and compactin. Pretreatment of the cells with nonlabelled LD lipoprotein resulted in a suppression of both the binding of 125I-labelled LD lipoprotein to the receptor and the synthesis of dolichyl saccharides from [14C]acetate and [3H]mannose, but not from [3H]mevalonolactone. Compactin, in contrast, inhibited only the formation of dolichol-linked oligosaccharides. Mevalonolactone (1 microM) abolished the inhibitory effect of LD lipoprotein on dolichyl saccharide formation, but was not able to restore the receptor-binding capacity, thus suggesting that the synthesis of lipoprotein receptor is not coupled to the formation of dolichyl saccharides.

Cells, Cultured↗
PubMed1995

Structure of heparin fragments with high affinity for lipoprotein lipase and inhibition of lipoprotein lipase binding to alpha 2-macroglobulin-receptor/low-density-lipoprotein-receptor-related protein by heparin fragments.

Heparin-derived deca- and octa-saccharides were subjected to affinity chromatography on lipoprotein lipase-Sepharose and the fractions eluted at high salt concentration were analysed by strong-anion-exchange chromatography. Two high-affinity decasaccharides were isolated and the structure determined by one- and two-dimensional 1H-n.m.r. spectroscopy. The affinities of 3H-labelled low-molecular-mass heparin and size-fractionated deca-, octa-, and hexa-saccharides for lipoprotein lipase immobilized on microtitre plates were determined from saturation curves. From competition experiments the affinities of unlabelled heparins and pure deca- and hexa-saccharide fragments were determined. The binding was size- and charge-dependent, but structural dependency was also indicated. Thus substitution of a 2-O-sulphated L-iduronic acid with D-glucuronic acid was less important than the sulphation pattern of the D-glucosamine residue for affinity for lipoprotein lipase. Heparin inhibits binding of lipoprotein lipase to alpha 2-macroglobulin-receptor/low-density-lipoprotein receptor-related protein. The effects of size, charge and structure for this inhibition were studied. The ability of the heparin fragments to inhibit binding correlated with their affinity for lipoprotein lipase. This indicates that the inhibition of the binding of lipoprotein lipase to alpha 2-macroglobulin-receptor/low-density-lipoprotein receptor-related protein by heparin is exclusively mediated by binding of heparin to lipoprotein lipase.

Amino Acid Sequence↗
PubMed2001

Lipoprotein-stimulated mesangial cell proliferation and gene expression are regulated by lipoprotein lipase.

BACKGROUND: Hyperlipidemia accelerates the progression of glomerular disease, and lipoproteins bind glomerular mesangial cells (MC) and induce proliferation and cytokine expression. In the vessel wall, the binding of lipoproteins to endothelial cells is markedly enhanced by lipoprotein lipase (LpL), synthesized by the underlying smooth muscle cells. While it is known that LpL is localized to the glomerulus, it is not known if and how it modulates the lipoprotein-mesangial interaction. METHODS: Very low-density lipoprotein (VLDL) was isolated from rats and was used to treat cultured primary rat MCs. Binding studies were done with and without LpL and with/without pretreatment with heparanase, which degrades cell surface heparan sulfate proteoglycan (HSPG), known to modulate the LpL-lipoprotein interaction in blood vessels. VLDL/LpL was also used to assess MC proliferation and gene expression of the cytokine platelet-derived growth factor (PDGF). RESULTS: LpL enhanced VLDL binding to MCs by as much as 200-fold, and most of this effect was blocked by pretreatment with heparanase. LpL amplified VLDL-driven MC proliferation and increased VLDL-induced PDGF expression. Heparanase pretreatment of cells eliminated both of these amplifications. LpL alone increased MC proliferation and PDGF gene expression. DISCUSSION: As in the vessel wall, LpL enhances VLDL binding to MCs. MCs respond to LpL binding by proliferating and expressing cytokines such as PDGF. LpL may be a crucial paracrine mediator of the glomerular response to circulating lipoproteins, amplifying a response that includes cytokine elaboration, influx of circulating monocytes, and eventual sclerosis.

Animals↗
PubMed2003

The low density lipoprotein receptor prevents secretion of dense apoB100-containing lipoproteins from the liver.

The assembly and secretion of very low density lipoproteins (VLDL) require microsomal triglyceride transfer protein (MTP). Recent evidence also suggests a role for the low density lipoprotein (LDL) receptor in this process. However, the relative importance of MTP in the two steps of VLDL assembly and the specific role of the LDL receptor still remain unclear. To further investigate the role of MTP and the LDL receptor in VLDL assembly, we bred mice harboring "floxed" Mttp alleles (Mttpflox/flox) and a Cre transgene on a low-density lipoprotein receptor-deficient background to generate mice with double deficiency in the liver (Ldlr-/- MttpDelta/Delta). In contrast to the plasma of Ldlr+/+ MttpDelta/Delta mice, the plasma of Ldlr-/- MttpDelta/Delta mice contained apoB100. Accordingly, Ldlr-/- MttpDelta/Delta but not Ldlr+/+ MttpDelta/Delta hepatocytes secreted apoB100-containing lipoprotein particles. The secreted lipoproteins were of LDL and HDL sizes but no VLDL-sized lipoproteins could be detected. These findings indicate that hepatic LDL receptors function as "gatekeepers" targeting dense apoB100-containing lipoproteins for degradation. In addition, these results suggest that very low levels of MTP are insufficient to mediate the second step but sufficient for the first step of VLDL assembly.

Alleles↗
PubMed1994

The protective role of high-density lipoprotein on oxidized-low-density-lipoprotein-induced U937/endothelial cell interactions.

The adherence of monocytes to the endothelium is an early event in atherogenesis. We have investigated this process by examining whether native and oxidized low-density and high-density lipoproteins could modulate this process. Only oxidized low-density lipoprotein caused a significant dose-dependent and time-dependent increase in U937 monocyte-like cell line binding to human endothelial cells, by a process which required de novo protein synthesis. Interestingly, E-selectin, intercellular adhesion molecule-1, vascular cell-adhesion molecule or P-selectin induction was not apparent in this system suggesting the presence of an alternative system for the interaction of endothelial cells with monocyte-like cells in response to oxidized low-density lipoprotein. High-density lipoprotein completely suppressed oxidized low-density-lipoprotein-induced adhesion of U937 cells to the endothelial monolayer, while oxidized high-density lipoprotein did not. These data suggest that the balance between native and oxidized lipoproteins may play a role in the formation of the atherosclerotic lesion by modulating monocyte endothelial interactions.

Base Sequence↗
PubMed1998

Plasma lipoprotein distribution of liposomal nystatin is influenced by protein content of high-density lipoproteins.

The plasma lipoprotein distribution of free nystatin (Nys) and liposomal nystatin (L-Nys) in human plasma samples with various lipoprotein lipid and protein concentrations and compositions was investigated. To assess the lipoprotein distributions of Nys and L-Nys, human plasma was incubated with Nys and L-Nys (equivalent to 20 microg/ml) for 5 min at 37 degreesC. The plasma was subsequently partitioned into its lipoprotein and lipoprotein-deficient plasma fractions by step-gradient ultracentrifugation, and each fraction was analyzed for Nys content by high-pressure liquid chromatography. The lipid and protein contents and compositions of each fraction were determined with enzymatic kits. Following the incubation of Nys and L-Nys in human plasma the majority of Nys recovered within the lipoprotein fractions was recovered from the high-density lipoprotein (HDL) fraction. Incorporation of Nys into liposomes consisting of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol significantly increased the percentage of drug recovered within the HDL fraction. Furthermore, it was observed that as the amount of HDL protein decreased the amounts of Nys and L-Nys recovered within this fraction decreased. These findings suggest that the preferential distribution of Nys and L-Nys into plasma HDL may be a function of the HDL protein concentration.

Anti-Bacterial Agents↗
PubMed1992

Regulation of lipoprotein lipase secretion in murine macrophages during foam cell formation in vitro. Effect of triglyceride-rich lipoproteins.

Triglyceride rich-lipoproteins induce triglyceride accumulation in macrophages, leading to foam cell formation. The correlation between cell triglyceride accumulation and lipoprotein lipase (LPL) secretion in murine macrophages and the role that LPL plays in the accumulation process were examined. LPL secretion is defined as the extracellular LPL activity that accumulates during a 4-hour incubation of treated and untreated cells in a bovine serum albumin-containing RPMI-1640 medium. LPL secretion was suppressed (up to 70%) in a dose- and time-dependent manner when J774.1 cells were incubated with chylomicrons, very low density lipoproteins, and intermediate density lipoproteins but not with low or high density lipoproteins from normolipidemic and hypertriglyceridemic subjects. Oleic acid both suppressed LPL secretion and invoked triglyceride accumulation. Suppression of LPL secretion preceded gross triglyceride accumulation, was reversible, and was not the result of a reduction in LPL mRNA. P388D1 cells neither secreted LPL nor accumulated triglyceride. Inhibition of LPL secretion by tunicamycin in both peritoneal macrophages and J774.1 cells prevented a hypertriglyceridemic very low density lipoprotein-induced triglyceride accumulation, an effect that was counteracted by addition of exogenous LPL. The results suggest that 1) extracellular hydrolysis of lipoprotein triglyceride is a major factor in inducing foam cell formation and 2) LPL secretion may be regulated by cell energy needs, and when these needs are exceeded, LPL secretion is suppressed.

Animals↗
PubMed1993

Relation between sex hormones and serum lipoprotein and lipoprotein(a) concentrations in premenopausal obese women.

Lipoprotein(a) (Lp[a]) is generally considered to be a risk factor for the development of cardiovascular disease, but little is known about the possible influence of obesity on the circulating levels of this lipoprotein. The present study was undertaken to examine this aspect in 136 menstrually active women by comparing the serum concentrations of Lp(a) between 72 obese and 64 age-matched nonobese women. Since an adverse effect of androgens and a protective effect of estrogens have been described for plasma lipoprotein profiles in obese women, the relation between the circulating levels of Lp(a) and those of these other hormones was also investigated in obese patients. In addition, other lipoproteins, anthropometric parameters (body mass index and waist-to-hip ratio), and insulin were evaluated. The levels of Lp(a) were not significantly different (Mann-Whitney U test chi 2, 3.59; p = 0.0582 [NS]) between obese (rank sum, 5,367) and control (rank sum, 3,949) women; in addition, the percentage of patients with high Lp(a) levels (cutoff defined at 30 mg/dL) did not differ between the two groups (obese women, 30%; control, 21.8%; chi 2, 0.90; two-sided p = 0.341 [NS]). Moreover, no correlation was found between Lp(a) and body mass index. Lastly, when the Lp(a) prevalence odds ratio for obesity was examined by adjusting the levels of this lipoprotein for age, triglycerides, total cholesterol, and high density lipoprotein cholesterol, the probability value (0.88) was far from significant. In obese women, no correlation was found between the logarithmically transformed Lp(a) concentrations and all the other variables evaluated in the study. In conclusion, the present study shows that the circulating levels of Lp(a) are not influenced by body weight and cardiovascular risk factors commonly associated with obesity, such as enhanced androgenic activity, hyperinsulinemia, adverse lipoprotein profile, and abdominal fat accumulation.

Adult↗
PubMedDate not supplied

Serum lipoprotein and lipoprotein lipase in overweight, type II diabetics during and after supplemented fasting.

Poorly controlled, obese, Type II diabetics were studied before, during, and 3 months after a weight reduction program that used supplemented fasting (200 kcal or 0.9 MJ/day). During fasting, the very low density lipoprotein (VLDL) triglycerides (TG) decreased, as did the adipose tissue lipoprotein lipase (AT-LPLA) and skeletal muscle lipoprotein lipase (SM-LPLA) activities. Three months later VLDL TG remained low (-59%), while high density lipoprotein cholesterol was higher (+11%) and blood glucose control improved compared with values on admission. The fractional removal rate (K2) at the i.v. fat tolerance test (IVFTT) and the SM-LPLA were unchanged, while AT-LPLA (expressed per gram of wet weight, but not as whole-body AT-LPLA) increased by 25%. There were no significant correlations between AT-LPLA and the lipoprotein TG concentrations or K2-IVFTT, although there were significant positive correlations between SM-LPLA and K2-IVFtt, both on admission and after body weight stabilization. This may indicate that SM-LPLA is more directly related to the capacity to remove lipoprotein TG, at least in obese diabetic patients. K2-IVFTT was inversely correlated to the VLDL TG and cholesterol concentrations both before and 3 months after fasting. Because both SM-LPLA and K2-IVFTT were unchanged after body weight reduction, the change in VLDL TG may be mainly due to a reduced rate of lipoprotein synthesis.

Adipose Tissue↗
PubMedDate not supplied

Enhanced lipoprotein lipase secretion from human monocyte-derived macrophages caused by hypertriglyceridemic very low density lipoproteins.

We studied the effects of very low density lipoprotein (VDL) obtained from hypertriglyceridemic subjects on the secretion of lipoprotein lipase and lipid accumulation in human monocyte-derived macrophages. The incubation of macrophages with VLDL obtained from different subjects caused different effects on the secretion of lipoprotein lipase (6.8 to 137.7 nM free fatty acid/min/mg cell protein) and triglyceride accumulation (184 to 507 micrograms/mg cell protein) in human monocyte-derived macrophages. VLDL from subjects with marked hypertriglyceridemia (approximately 1000 mg/dl) had a fourfold greater effect on lipoprotein lipase activity and a twofold greater effect on cellular triglyceride accumulation when compared with the effects of VLDL from normolipidemic subjects. Both lipoprotein lipase activity and triglyceride accumulation correlated positively with plasma VLDL triglyceride levels (r = 0.50 and 0.45, respectively, p less than 0.05). From these data, we suggest that the activity of lipoprotein lipase secreted from macrophages incubated with VLDL was dependent on triglyceride concentrations, and that the secretion of lipoprotein lipase enhanced by hypertriglyceridemic VLDL was closely related to the intracellular accumulation of triglyceride.

Cell Line↗
PubMed1999

Treatment of obese subjects with the oral growth hormone secretagogue MK-677 affects serum concentrations of several lipoproteins, but not lipoprotein(a).

Obesity is associated with blunted GH secretion and an unfavorable lipoprotein pattern. The objective of this study was to investigate the effects of treatment with the oral GH secretagogue MK-677 on lipoproteins in otherwise healthy obese males. The study was randomized, double blind, and parallel. Twenty-four obese males, aged 18-50 yr, with body mass index greater than 30 kg/m2 and waist/hip ratio above 0.95 were treated with 25 mg MK-677 (n = 12) or placebo (n = 12) daily for 8 weeks. MK-677 treatment did not significantly change serum lipoprotein(a) [Lp(a)] levels. Serum apolipoprotein A-I and E (apoA-I and apoE) were increased at 2 weeks (P < 0.001 and P < 0.01 vs. placebo, respectively), but were not changed at study end. Serum total cholesterol and low density lipoprotein (LDL) cholesterol (LDL-C) levels were not significantly changed by MK-677 treatment. Serum high density lipoprotein (HDL) cholesterol (HDL-C) was increased at 2 weeks of MK-677 treatment (P < 0.01 vs. placebo), but not at 8 weeks. The LDL-C/HDL-C ratio was reduced after 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Mean LDL particle diameter was decreased at 2 weeks (P < 0.05 vs. placebo), but was unchanged compared with baseline values at 8 weeks (P = NS vs. placebo). The level of serum triglycerides was increased at 2 (P < 0.05 vs. placebo), but not at 8, weeks. Lipoprotein lipase activity in abdominal and gluteal sc adipose tissue was not affected by active treatment. In conclusion, treatment with the oral GH secretagogue MK-677 affected circulating lipoproteins. The effects on serum apoA-1, apoE, triglycerides, and mean LDL particle diameter were transient. At study end, the LDL-C/HDL-C ratio was decreased. MK-677 treatment did not significantly affect serum Lp(a) concentrations at the present dose and administration protocol.

Adipose Tissue↗