Triacylglycerol-rich lipoproteins alter the secretion, and the cholesterol-effluxing function, of apolipoprotein E-containing lipoprotein particles from human (THP-1) macrophages

2001 ◽  
Vol 356 (2) ◽  
pp. 515-523 ◽  
Author(s):  
E. Marie LINDHOLM ◽  
Anna M. PALMER ◽  
Annette GRAHAM
Keyword(s):  
Apolipoprotein E ◽  
Type Ii Diabetes ◽  
Cholesterol Efflux ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Content ◽  
Type Ii ◽  
Increased Risk ◽  
Triacylglycerol Accumulation ◽  
Dose Dependent

Elevated plasma levels of triacylglycerol-rich lipoproteins (TGRLP) are associated with increased risk of atherogenesis and abnormal reverse cholesterol transport, as illustrated in Type II diabetes. Here we examine the effect of plasma triacylglycerol-rich or cholesteryl ester-rich lipoproteins on the secretion of nascent apolipoprotein E (apoE)-containing lipoprotein E (LpE) particles by human (THP-1) macrophages. As expected, preincubation with low-density lipoprotein (LDL) yielded small but significant increases in total cellular cholesterol content and also the secretion of apoE by macrophages. By contrast, preincubation with TGRLP resulted in higher, dose-dependent, increases in apoE secretion that reflected, but were not dependent on, cellular triacylglycerol accumulation. Secreted apoE was incorporated into a pre-β migrating LpE fraction that differed in lipid composition and flotation density depending on preincubation conditions. Specifically, the LpE-containing lipoprotein fraction produced by macrophages preincubated with TGRLP was cholesterol-poor, markedly heterogeneous and of higher peak flotation density (d 1.14–1.18) when compared with particles produced after preincubation with LDL. Both the conditioned medium and the isolated (d < 1.21) LpE-containing fraction, yielded by macrophages preincubated with TGRLP, seemed poorer at inducing cholesterol efflux than the equivalent fractions from cells preincubated with LDL, as judged by [3H]cholesterol efflux from untreated ‘naïve’ macrophages. Thus, although the interaction of TGRLP with macrophages can enhance apoE output from these cells, the LpE particles produced seem to be relatively inefficient mediators of cholesterol efflux. These factors might contribute to the increased risk of atherosclerosis in individuals with Type II diabetes.

scholarly journals Synergistic Hypoglycemic Effects of Pumpkin Polysaccharides and Puerarin on Type II Diabetes Mellitus Mice

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 955 ◽  
Author(s):  
Xue Chen ◽  
Lei Qian ◽  
Bujiang Wang ◽  
Zhijun Zhang ◽  
Han Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type Ii Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Type Ii Diabetes Mellitus ◽  
Hypoglycemic Effect ◽  
Lipid Lowering ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Type Ii

To investigate the hypoglycemic effect and potential mechanism of pumpkin polysaccharides and puerarin on type II diabetes mellitus (T2DM) mice, mice were fed a high-fat diet and injected intraperitoneally with streptozotacin to induce T2DM. After eight weeks of drug administration, blood samples were withdrawn from tail veins of mice that had been fasted overnight. The results showed that both pumpkin polysaccharides and puerarin, as well as a pumpkin polysaccharides and puerarin combination, could ameliorate T2DM. The pumpkin polysaccharides and puerarin combination had a synergetic hypoglycemic effect on T2DM mice that was greater than the pumpkin polysaccharides’ or the puerarin’s hypoglycemic effect. Both the pumpkin polysaccharides and the puerarin were found to ameliorate the blood glucose tolerance and insulin resistance of T2DM mice. They showed lipid-lowering activity by reducing the total cholesterol, triglycerides, and low-density lipoprotein levels, and improving the high-density lipoprotein level. They had beneficial effects on the oxidative stress by decreasing the reactive oxygen species and malondialdehyde levels, and increasing the glutathione level and the superoxide dismutase activity. Furthermore, the nuclear factor E2 related factor 2 (Nrf2), heme oxygenase-1, and phosphoinositide-3-kinase (PI3K) levels were upregulated, and the Nrf2 and PI3K signalling pathways might be involved in the hypoglycemic mechanism. The combined administration of pumpkin polysaccharides and puerarin could synergistically ameliorate T2DM.

Paraoxonase-1 (PON-1) genotype and activity and in vivo oxidized plasma low-density lipoprotein in Type II diabetes

2005 ◽  
Vol 109 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Mike J. Sampson ◽  
Simon Braschi ◽  
Gavin Willis ◽  
Sian B. Astley
Keyword(s):  
Type Ii Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Ldl Oxidation ◽  
Phenyl Acetate ◽  
Low Density ◽  
Type Ii

The HDL (high-density lipoprotein)-associated enzyme PON (paraoxonase)-1 protects LDL (low-density lipoprotein) from oxidative modification in vitro, although it is unknown if this anti-atherogenic action occurs in vivo. In a cross-sectional study of 58 Type II diabetic subjects and 50 controls, we examined the fasting plasma LDL basal conjugated diene concentration [a direct measurement of circulating oxLDL (oxidatively modified LDL)], lipoprotein particle size by NMR spectroscopy, PON-1 polymorphisms (coding region polymorphisms Q192R and L55M, and gene promoter polymorphisms −108C/T and −162G/A), PON activity (with paraoxon or phenyl acetate as the substrates) and dietary antioxidant intake. Plasma oxLDL concentrations were higher in Type II diabetic patients (males, P=0.048; females, P=0.009) and unrelated to NMR lipoprotein size, PON-1 polymorphisms or PON activity (with paraoxon as the substrate) in any group. In men with Type II diabetes, however, there was a direct relationship between oxLDL concentrations and PON activity (with phenyl acetate as the substrate; r=0.611, P=0.0001) and an atherogenic NMR lipid profile in those who were PON-1 55LL homozygotes. Circulating oxLDL concentrations in vivo were unrelated to PON-1 genotypes or activity, except in male Type II diabetics where there was a direct association between PON activity (with phenyl acetate as the substrate) and oxLDL levels. These in vivo data contrast with in vitro data, and may be due to confounding by dietary fat intake. Male Type II diabetic subjects with PON-1 55LL homozygosity have an atherogenic NMR lipid profile independent of LDL oxidation. These data do not support an in vivo action of PON on LDL oxidation.

scholarly journals Evaluation of Serum HDL and LDL levels in Type II Diabetes Mellitus

2013 ◽  
Vol 1 (1) ◽  
pp. 21 ◽  
Author(s):  
K R Joshi ◽  
K K Hiremath ◽  
S P Gupta
Keyword(s):  
Diabetes Mellitus ◽  
Type Ii Diabetes ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Type Ii Diabetes Mellitus ◽  
Lipoprotein Cholesterol ◽  
Control Group ◽  
Type Ii

  Introduction: Diabetes mellitus is a type of metabolic disorder characterized by hyperglycemia resulting from defect in insulin secretion, insulin action or both. This study intended to compare High Density Lipoprotein Cholesterol (HDL) and Low Density Lipoprotein Cholesterol (LDL) profile between type II diabetic and non-diabetic subjects and also find the correlation between HDL and LDL cholesterol in type II diabetic.   Methods: The study was conducted on 100 total subjects out of which experimental group with 50 subjects of known Type II Diabetes mellitus and control group with 50 subjects.   Results: The result of the present study suggests that fasting blood sugar and LDL cholesterol levels were increased but HDL cholesterol level was reduced in type II diabetic subjects when compared to controls.   Conclusion: The estimation of HDL cholesterol and LDL cholesterol in type II diabetes mellitus is very useful as it may serve as a useful parameter to monitor the prognosis of the patient.

scholarly journals Baseline cardiometabolic profiles and SARS-CoV-2 infection in the UK Biobank

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0248602 ◽  
Author(s):  
Ryan J. Scalsky ◽  
Yi-Ju Chen ◽  
Karan Desai ◽  
Jeffery R. O’Connell ◽  
James A. Perry ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type Ii Diabetes ◽  
Cardiometabolic Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Type Ii ◽  
Uk Biobank ◽  
The Uk ◽  
The Impact

Background SARS-CoV-2 is a rapidly spreading coronavirus responsible for the Covid-19 pandemic, which is characterized by severe respiratory infection. Many factors have been identified as risk factors for SARS-CoV-2, with much early attention being paid to body mass index (BMI), which is a well-known cardiometabolic risk factor. Objective This study seeks to examine the impact of additional baseline cardiometabolic risk factors including high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), Apolipoprotein A-I (ApoA-I), Apolipoprotein B (ApoB), triglycerides, hemoglobin A1c (HbA1c) and diabetes on the odds of testing positive for SARS-CoV-2 in UK Biobank (UKB) study participants. Methods We examined the effect of BMI, lipid profiles, diabetes and alcohol intake on the odds of testing positive for SARS-Cov-2 among 9,005 UKB participants tested for SARS-CoV-2 from March 16 through July 14, 2020. Odds ratios and 95% confidence intervals were computed using logistic regression adjusted for age, sex and ancestry. Results Higher BMI, Type II diabetes and HbA1c were associated with increased SARS-CoV-2 odds (p < 0.05) while HDL-C and ApoA-I were associated with decreased odds (p < 0.001). Though the effect of BMI, Type II diabetes and HbA1c were eliminated when HDL-C was controlled, the effect of HDL-C remained significant when BMI was controlled for. LDL-C, ApoB and triglyceride levels were not found to be significantly associated with increased odds. Conclusion Elevated HDL-C and ApoA-I levels were associated with reduced odds of testing positive for SARS-CoV-2, while higher BMI, type II diabetes and HbA1c were associated with increased odds. The effects of BMI, type II diabetes and HbA1c levels were no longer significant after controlling for HDL-C, suggesting that these effects may be mediated in part through regulation of HDL-C levels. In summary, our study suggests that baseline HDL-C level may be useful for stratifying SARS-CoV-2 infection risk and corroborates the emerging picture that HDL-C may confer protection against sepsis in general and SARS-CoV-2 in particular.

scholarly journals Activation of the TLR4 signaling pathway and abnormal cholesterol efflux lead to emphysema in ApoE-deficient mice

2012 ◽  
Vol 302 (11) ◽  
pp. L1200-L1208 ◽  
Author(s):  
Monica Goldklang ◽  
Polina Golovatch ◽  
Tina Zelonina ◽  
Jordis Trischler ◽  
Daniel Rabinowitz ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Oxidized Ldl ◽  
Interleukin 1 ◽  
Low Density Lipoprotein ◽  
Airflow Obstruction ◽  
Density Lipoprotein ◽  
Atherogenic Diet ◽  
Lung Damage ◽  
Increased Risk ◽  
Density Lipoprotein Receptor

Smokers with airflow obstruction have an increased risk of atherosclerosis, but the relationship between the pathogenesis of these diseases is not well understood. To determine whether hypercholesterolemia alters lung inflammation and emphysema formation, we examined the lung phenotype of two hypercholesterolemic murine models of atherosclerosis at baseline and on a high-fat diet. Airspace enlargement developed in the lungs of apolipoprotein E-deficient (Apoe −/− ) mice exposed to a Western-type diet for 10 wk. An elevated number of macrophages and lymphocytes accompanied by an increase in matrix metalloproteinase-9 (MMP-9) activity and MMP-12 expression was observed in the lungs of Apoe −/− mice on a Western-type diet. In contrast, low-density lipoprotein receptor-deficient ( Ldlr −/−) mice did not exhibit lung destruction or inflammatory changes. Most importantly, we revealed augmented expression of the downstream targets of the Toll-like receptor (TLR) pathway, interleukin-1 receptor-associated kinase 1, and granulocyte colony-stimulating factor, in the lungs of Apoe −/− mice fed with a Western-type diet. In addition, we demonstrated overexpression of MMP-9 in Apoe −/− macrophages treated with TLR4 ligand, augmented with the addition of oxidized LDL, suggesting that emphysema in these mice results from the activation of the TLR pathway secondary to known abnormal cholesterol efflux. Our findings indicate that, in Apoe −/− mice fed with an atherogenic diet, abnormal cholesterol efflux leads to increased systemic inflammation with subsequent lung damage and emphysema formation.

scholarly journals Deletion of the Mir-106b~ 25 MicroRNA cluster attenuates atherosclerosis in Apolipoprotein E knockout mice

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Jonathan Semo ◽  
Gil Chernin ◽  
Michael Jonas ◽  
Sara Shimoni ◽  
Jacob George
Keyword(s):  
Apolipoprotein E ◽  
Knockout Mice ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Content ◽  
Lesion Size ◽  
Low Density ◽  
Microrna Cluster ◽  
Apoe Ko Mice ◽  
Apoe Ko

Abstract Background MicroRNAs are short non-coding RNAs that regulate gene expression. The aim of this study was to gain an understanding of the possible role of the miR-106b~ 25 microRNA cluster in regulating atherosclerosis in mice. Methods MiR-106b~ 25 knockout mice were outcrossed into Apolipoprotein E (ApoE) knockout background to generate double knockout mice. At 36 weeks of age, lesion size was evaluated in the aortic sinus by oil-red-O staining. Results Lesion size was 2-fold smaller in double KO mice in comparison to ApoE KO mice. In addition, collagen staining showed a trend towards a stable plaque phenotype in the double KO mice. Lipid profiling of plasma samples of double KO and ApoE KO mice using FPLC revealed over 2-fold decrease in Very low density lipoprotein (VLDL) cholesterol content and a 50% decrease in low density lipoprotein (LDL) cholesterol content in double KO mice. By using target prediction software, we have identified several possible targets for the miR-106b~ 25 cluster including the VLDL and LDL receptors. We found that upon feeding miR-106b~ 25 KO mice with high fat diet, the expression of LDL and VLDL receptors was higher than in the wild-type mice, suggesting the miR-106b~ 25 cluster regulates atherosclerosis by influencing clearance of VLDL and LDL from the plasma. Conclusions We identified the miR-106b~ 25 cluster as a novel regulator of atherosclerosis in ApoE KO mice, presumably by regulating plasma cholesterol levels.

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