scholarly journals Increased response to cholesterol feeding in apolipoprotein C1-deficient mice

1995 ◽  
Vol 305 (3) ◽  
pp. 905-911 ◽  
Author(s):  
J H van Ree ◽  
M H Hofker ◽  
W J A A van den Broek ◽  
J M A van Deursen ◽  
H van der Boom ◽  
...  
Keyword(s):  
Serum Cholesterol ◽  
Embryonic Stem ◽  
Density Lipoprotein ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Low Density ◽  
Remnant Lipoproteins ◽  
Deficient Mice

The function of apolipoprotein (apo) C1 in vivo is not well understood. From in vitro studies it has been reported that an excess of apoC1 relative to apoE inhibits receptor-mediated uptake of remnant lipoproteins [Sehayek and Eisenberg (1991) J. Biol. Chem. 266, 22453-22459]. In order to gain a better understanding of the role of apoC1 in lipoprotein metabolism in vivo, we have generated apoC1-deficient mice by gene targeting in embryonic stem cells. Homozygous mutant mice are viable and do not show overt abnormalities. Serum triacylglycerol levels are increased by 60% on both a standard mouse diet and a mild hypercholesterolaemic diet compared with controls. Total serum cholesterol levels are similar to controls on the two diets. However, the level of high-density lipoprotein cholesterol in the apoC1-deficient mice fed on the mild hypercholesterolaemic diet is slightly decreased, which is accompanied by a 3-fold increase in very-low-density plus low-density lipoprotein (VLDL+LDL) cholesterol. On a severe atherogenic diet, the homozygous apoC1-deficient mice become hypercholesterolaemic, with a serum cholesterol level of 10.7 +/- 3.3 mM compared with 6.7 +/- 1.8 mM and 5.1 +/- 1.6 mM in heterozygous and control mice respectively. The increase in cholesterol is mainly confined to the VLDL+LDL-sized fractions. Binding experiments revealed that lipoproteins lacking apoC1 with d < 1.006 g/ml are poor competitors for 125I-labelled LDL binding to the LDL receptor on HepG2 cells. This suggests that total apoC1 deficiency leads to impaired receptor-mediated clearance of remnant lipoproteins rather than enhanced uptake, as was expected from data reported in the literature.

Effect of serum lipoprotein(a) on estimation of low-density lipoprotein cholesterol by the Friedewald formula

1994 ◽  
Vol 40 (4) ◽  
pp. 571-573 ◽  
Author(s):  
K M Li ◽  
D E Wilcken ◽  
N P Dudman
Keyword(s):  
Serum Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein A ◽  
Friedewald Formula

Abstract The calculation of serum low-density lipoprotein cholesterol (LDL-C) by the Friedewald formula does not account for the cholesterol associated with lipoprotein(a) [Lp(a)]. To quantify the contribution of Lp(a) cholesterol to total serum cholesterol, we measured concentrations of serum Lp(a) by an ELISA and concentrations of other serum lipids and lipoproteins by standard assays in 23 normolipemic women, ages 50-60 years. In measuring serum high-density lipoprotein we found that polyethylene glycol 6000 precipitated &gt; 99.8% of all Lp(a). When serum Lp(a) concentrations were &lt; or = 300 mg/L, 301-600 mg/L, and &gt; 600 mg/L, the uncorrected serum LDL-C was overestimated, respectively, by a mean of 4.1% (n = 7), 8.5% (n = 8), and 21.4% (n = 8). Serum Lp(a) concentrations were positively correlated with percentage overestimation (P &lt; 0.001), but were not correlated with either corrected or uncorrected serum LDL-C. We conclude that the Friedewald formula should be modified to take into account the contribution of Lp(a) cholesterol to total serum cholesterol.

scholarly journals Reduced very-low-density lipoprotein fractional catabolic rate in apolipoprotein C1-deficient mice

1997 ◽  
Vol 321 (2) ◽  
pp. 445-450 ◽  
Author(s):  
Miek C. JONG ◽  
Janine H. van REE ◽  
Vivian E. H. DAHLMANS ◽  
Rune R. FRANTS ◽  
Marten H. HOFKER ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Fractional Catabolic Rate ◽  
Catabolic Rate ◽  
And Control ◽  
Deficient Mice

The function of apolipoprotein (apo) C1 in vivo is not clearly defined. Because transgenic mice overexpressing human apoC1 show elevated triacylglycerol (TG) levels [Simonet, Bucay, Pitas, Lauer and Taylor (1991) J. Biol. Chem. 266, 8651Ő8654], an as yet unknown role for apoC1 in TG metabolism has been suggested. Here we investigated directly the effect of the complete absence of apoC1 on very-low-density lipoprotein (VLDL)-TG lipolysis, clearance and production, by performing studies with the previously generated apoC1-deficient mice. On a sucrose-rich, low fat/low cholesterol (LFC) diet, apoC1-deficient mice accumulate in their circulation VLDL particles, which contain relatively lower amounts of lipids when compared with VLDL isolated from control mice. Lipolysis assays in vitro on VLDL from apoC1-deficient and control mice showed no differences in apparent Km and Vmax values (0.27ŷ0.06 versus 0.24ŷ0.03 mmol of TG/litre and 0.40ŷ0.03 versus 0.36ŷ0.03 mmol of non-esterified fatty acid (NEFA)/min per litre respectively). To correct for potential differences in the size of the VLDL particles, the resulting Km values were also expressed relative to apoB concentration. Under these conditions apoC1-deficient VLDL displayed a lower, but not significant, Km value when compared with control VLDL (3.44ŷ0.71 versus 4.44ŷ0.52 mmol of TG2/g apoB per litre). VLDL turnover studies with autologous injections of [3H]TG-VLDL in vivo showed that the VLDL fractional catabolic rate (FCR) was decreased by up to 50% in the apoC1-deficient mice when compared with control mice (10.5ŷ3.4 versus 21.0ŷ1.2/h of pool TG). No significant differences between apoC1-deficient and control mice were observed in the hepatic VLDL production estimated by Triton WR139 injections (0.19ŷ0.02 versus 0.21ŷ0.05 mmol/h of TG per kg) and in the extra-hepatic lipolysis of VLDL-TG (4.99ŷ1.62 versus 3.46ŷ1.52/h of pool TG) in vivo. Furthermore, [125I]VLDLŐapoB turnover experiments in vivo also showed a 50% decrease in the FCR of VLDL in apoC1-deficient mice when compared with control mice on the LFC diet (1.1ŷ0.3 versus 2.1ŷ0.1/h of pool apoB). When mice were fed a very high fat/high cholesterol (HFC) diet, the VLDLŐapoB FCR was further decreased in apoC1-deficient mice (0.4ŷ0.1 versus 1.4ŷ0.4/h of pool apoB). We conclude that, in apoC1-deficient mice, the FCR of VLDL is reduced because of impaired uptake of VLDL remnants by hepatic receptors, whereas the production and lipolysis of VLDL-TG is not affected.

Tracking of Serum Cholesterol and Lipoprotein Levels From the First Year of Life

PEDIATRICS ◽  
1993 ◽  
Vol 91 (5) ◽  
pp. 949-954
Author(s):  
Markku J. T. Kallio ◽  
Leena Salmenperä ◽  
Martti A. Siimes ◽  
Jaakko Perheentupa ◽  
Tatu A. Miettinen
Keyword(s):  
Serum Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Concentration ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
First Year ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
First Year Of Life

Objective. To examine the development of tracking of serum cholesterol concentration from birth to childhood. Design. In a longitudinal study of healthy children, concentrations of total serum cholesterol and triglyceride were determined at birth (n = 193); at 2 (n = 192), 4 (n = 192), 6 (n = 190), 7.5 (n = 118), 9 (n = 188), and 12 months (n = 196); and at 5 years of age (n = 162). Concentrations of cholesterol—very-low-density lipoprotein, low-density lipoprotein, high-density lipoprotein-2 (HDL2), and HDL3—were determined at 2, 6, 9, and 12 months (n = 36) and at 5 years (n = 162). Results. The correlation coefficients of total cholesterol levels during the first year of life with the level at 5 years of age were as follows: at birth .04, at 2 months .36 (P &lt; .001), at 4 months .26 (P &lt; .001), at 6 months .28 (P &lt; .001), at 7.5 months .25 (P &lt; .001), at 9 months .35 (P &lt; .001), and at 12 months .48 (P &lt; .001). The correlation for exclusively breast-fed children between 6 months and 5 years of age was r = .37, P &lt; .001, while that for children receiving partially breast milk, formula, or solid foods was r = .12, P = not significant (NS), and between 9 months and 5 years r = .38, P &lt; .01, and r = .28, P &lt; .05, respectively. The correlation coefficients of the lipoprotein levels between ages 12 months and 5 years were as follows: low-density lipoprotein cholesterol .58 (P &lt; .001), total HDL cholesterol .30 (P &lt; .05), HDL2 cholesterol .34 (P &lt; .05), HDL3 cholesterol .17 (P = NS), very-low-density lipoprotein cholesterol .24 (P = NS), total triglyceride .37 (P &lt; .05), and triglyceride-very-low-density lipoprotein .37 (P &lt; .05). Of the children whose total serum cholesterol level was above the 90th percentile at birth, or at 2, 4, 6, 7.5, 9, or 12 months, 6%, 35%, 29%, 30%, 31%, 33%, and 45%, respectively, were above the 90th percentile at 5 years of age. In retrospect, 45% of the children whose serum cholesterol level was above the 90th percentile at 5 years were above the 90th percentile at the age of 12 months and 80% were in the highest quartile. Conclusions. The results indicate that tracking of serum cholesterol concentration during the first year of life is stronger when examining children who are receiving a relatively homogenous diet, such as exclusive breast-feeding, and weaker as children are weaned to formula and solid foods. After the weaning process is completed, children's relative serum cholesterol levels have become established and the tracking of serum cholesterol is of the same magnitude as for older children and adolescents.

Activity of low-density lipoprotein receptors as estimated from concentrations of apolipoprotein B and C-II in serum.

1988 ◽  
Vol 34 (11) ◽  
pp. 2224-2227 ◽  
Author(s):  
H Ito ◽  
C Naito ◽  
H Hayashi ◽  
M Kawamura
Keyword(s):  
Serum Cholesterol ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Receptor Activity ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Low Density ◽  
Apo B ◽  
Apo E

Abstract The correlation between low-density lipoprotein (LDL) receptor activity and concentrations of lipids and apolipoproteins in serum was examined in 12 subjects with heterozygous familial hypercholesterolemia (FH) and in four with non-FH type II hyperlipoproteinemia. Concentrations of high-density lipoprotein cholesterol and of apolipoproteins (apo) A-I, C-II, and C-III were significantly positively correlated with LDL receptor activity, whereas LDL receptor activity was significantly inversely correlated with LDL cholesterol and apo B concentrations, and with apo ratios B/A-I and B/A-II. Neither total serum cholesterol, triglyceride, phospholipid, apo A-I, nor apo E concentrations correlated significantly with LDL receptor activity. Multiple regression analysis, with LDL receptor activity as the dependent variable, revealed concentrations of apo B and apo C-II to be the principal determinant factors. To confirm this, we subsequently calculated the LDL receptor activities before and after administration of CS-514, an inhibitor of hydroxymethylglutaryl-CoA reductase (EC 1.1.1.88), which increases the hepatic LDL receptor activity and decreases the concentration of cholesterol in serum. This drug increased calculated LDL receptor activities significantly, with a significant decrease in serum cholesterol.

scholarly journals Effect of antihyperlipidemic polyherbal formulation in high diet induced hyperlipidemia wistar albino rats. An in vitro - in vivo evaluation

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1531-1538
Author(s):  
Smitha Rani ◽  
Manju Sreedharan Nair Leelabai Amma ◽  
Sarada Nallani Chakravarthula
Keyword(s):  
Total Serum ◽  
Albino Rats ◽  
Total Serum Cholesterol ◽  
Low Density ◽  
Polyherbal Formulation ◽  
Anti Oxidant ◽  
In Vivo Analysis ◽  
Wistar Albino Rats

Hyperlipidemia is a prevalent global health problem, and it is linked to various cardiovascular disorders. The side effects of the current lipid-lowering drugs have increased the tendency to move toward traditional and alternative remedies. The study aims to Formulate and evaluate the Antilipidemic activity of Polyherbal formulations used as a traditional medicine in the Malabar area, Kerala by in vitro and in vivo methods. Further, the present study also compares the impact of seasonal variations on chemical contents of ingredient herbs of polyherbal medicine. They were analyzed for, anti-oxidant activity by DPPH and Nitric oxide method and In-vitro anti-cholesterol activity by cholesterol enzymatic endpoint method using simavastatin as a positive control. The formulation showing highest anti-oxidant and in- vitro Antilipidemic activity was selected for in-vivo analysis. Out of four formulations, PHF 1 shows low IC50  values in DPPH and Nitric oxide methods (250.45± 0.60, 985.40±5.59), respectively. The in-vitro anti-cholesterol activity showed a maximum % of inhibition for PHF1. Based on this PHF 1was selected for in vivo analysis. Acute toxicity was performed according to OECD guidelines. The antilipidemic activity was conducted by  Diet-induced hyperlipidemia model in Wistar albino rats, containing six animals in each group. All the groups except saline control received a high-fat diet for two weeks. The Polyherbal formulation (200 mg/kg & 400 mg/kg) showed significant (P<0.05) reduction in total serum cholesterol and lipid levels compared to the vehicle control group. This present study proved that Polyherbal formulation has Antilipidemic activity against the diet-induced hyperlipidemia model by reducing the total serum cholesterol (TC), triglycerides (TG), very low-density lipid (VLDL), low-density lipids(LDL) levels and increasing high-density lipid (HDL) level.

scholarly journals Reductions of copper ion-mediated low-density lipoprotein (LDL) oxidations of trypsin inhibitors, the sweet potato root major proteins, and LDL binding capacities

2020 ◽  
Vol 61 (1) ◽  
Author(s):  
Yeh-Lin Lu ◽  
Chia-Jung Lee ◽  
Shyr-Yi Lin ◽  
Wen-Chi Hou
Keyword(s):  
Sweet Potato ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Trypsin Inhibitors ◽  
Water Soluble ◽  
Affinity Column ◽  
Low Density ◽  
Native Page

Abstract Background The root major proteins of sweet potato trypsin inhibitors (SPTIs) or named sporamin, estimated for 60 to 80% water-soluble proteins, exhibited many biological activities. The human low-density lipoprotein (LDL) showed to form in vivo complex with endogenous oxidized alpha-1-antitrypsin. Little is known concerning the interactions between SPTIs and LDL in vitro. Results The thiobarbituric-acid-reactive-substance (TBARS) assays were used to monitor 0.1 mM Cu2+-mediated low-density lipoprotein (LDL) oxidations during 24-h reactions with or without SPTIs additions. The protein stains in native PAGE gels were used to identify the bindings between native or reduced forms of SPTIs or soybean TIs and LDL, or oxidized LDL (oxLDL). It was found that the SPTIs additions showed to reduce LDL oxidations in the first 6-h and then gradually decreased the capacities of anti-LDL oxidations. The protein stains in native PAGE gels showed more intense LDL bands in the presence of SPTIs, and 0.5-h and 1-h reached the highest one. The SPTIs also bound to the oxLDL, and low pH condition (pH 2.0) might break the interactions revealed by HPLC. The LDL or oxLDL adsorbed onto self-prepared SPTIs-affinity column and some components were eluted by 0.2 M KCl (pH 2.0). The native or reduced SPTIs or soybean TIs showed different binding capacities toward LDL and oxLDL in vitro. Conclusion The SPTIs might be useful in developing functional foods as antioxidant and nutrient supplements, and the physiological roles of SPTIs-LDL and SPTIs-oxLDL complex in vivo will investigate further using animal models.

scholarly journals Generation and Characterization of Smac/DIABLO-Deficient Mice

2002 ◽  
Vol 22 (10) ◽  
pp. 3509-3517 ◽  
Author(s):  
Hitoshi Okada ◽  
Woong-Kyung Suh ◽  
Jianping Jin ◽  
Minna Woo ◽  
Chunying Du ◽  
...  
Keyword(s):  
Physiological Function ◽  
Es Cells ◽  
Embryonic Stem ◽  
Caspase Activation ◽  
Proapoptotic Protein ◽  
Apoptosis Proteins ◽  
Deficient Mice

ABSTRACT The mitochondrial proapoptotic protein Smac/DIABLO has recently been shown to potentiate apoptosis by counteracting the antiapoptotic function of the inhibitor of apoptosis proteins (IAPs). In response to apoptotic stimuli, Smac is released into the cytosol and promotes caspase activation by binding to IAPs, thereby blocking their function. These observations have suggested that Smac is a new regulator of apoptosis. To better understand the physiological function of Smac in normal cells, we generated Smac-deficient (Smac−/− ) mice by using homologous recombination in embryonic stem (ES) cells. Smac−/− mice were viable, grew, and matured normally and did not show any histological abnormalities. Although the cleavage in vitro of procaspase-3 was inhibited in lysates of Smac−/− cells, all types of cultured Smac−/− cells tested responded normally to all apoptotic stimuli applied. There were also no detectable differences in Fas-mediated apoptosis in the liver in vivo. Our data strongly suggest the existence of a redundant molecule or molecules capable of compensating for a loss of Smac function.

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