scholarly journals Hepatic lipase function and the accumulation of β-very-low-density lipoproteins in the plasma of cholesterol-fed rabbits

1993 ◽  
Vol 293 (3) ◽  
pp. 745-750 ◽  
Author(s):  
S Chang ◽  
J Borensztajn
Keyword(s):  
Lipoprotein Lipase ◽  
Hepatic Lipase ◽  
Low Density Lipoproteins ◽  
High Cholesterol Diet ◽  
Low Density ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat ◽  
Very Low Density Lipoproteins

The accumulation of cholesterol-rich beta-very-low-density lipoproteins (beta-VLDL) in the plasma of rabbits fed on a high-fat high-cholesterol diet is due to a defect in the clearance of these lipoprotein remnants from circulation by the liver. In view of the evidence that hepatic lipase participates in the process of rapid removal of remnants from circulation, and considering that rabbits are naturally deficient in hepatic lipase, we examined whether this defect in the clearance of beta-VLDL could be reversed by exogenous hepatic lipase. We report that treatment in vitro of [3H]cholesterol-labelled beta-VLDL, or rat chylomicrons, with hepatic lipase resulted in the formation of particles that were rapidly cleared from circulation by the liver when injected intravenously into hypercholesterolaemic rabbits. These results are consistent with the notion that, in addition to the well-established requirement for lipoprotein lipase activity, the generation of remnants capable of being efficiently taken up by the liver also requires the action of hepatic lipase. Lipoprotein lipase acts on triacylglycerol-rich lipoproteins to transform them into particles (remnants) which bind to the surface of liver cells, where they become accessible to hepatic lipase. Hepatocyte endocytosis of these remnants occurs only after further modification by hepatic lipase. According to this scheme, the results presented suggest that the accumulation of beta-VLDL in the circulation of rabbits fed on a high-fat high-cholesterol diet is the result of the saturation of the available hepatic lipase by abnormally high levels of lipoprotein-lipase-generated chylomicron remnants.

Abstract 130: Hypercholesterolemia Suppresses Carotid Artery Endothelial NOS3 Expression via Epigenetic Mechanisms

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Alex Sotolongo ◽  
Yi-Zhou Jiang ◽  
John Karanian ◽  
William Pritchard ◽  
Peter Davies
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Endothelial Cells ◽  
Dna Methyltransferase ◽  
Control Group ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat

Objective: One of the first clinically detectable changes in the vasculature during atherogenesis is the accumulation of cholesterol within the vessel wall. Hypercholesterolemia is characterized by dysfunctional endothelial-dependent vessel relaxation and impaired NOS3 function. Since DNA methylation at gene promoter regions strongly suppresses gene expression, we postulated that high-fat/high-cholesterol diet suppresses endothelial NOS3 through promoter DNA methylation. Methods: Domestic male pigs were fed control diet (CD) or isocaloric high fat and high cholesterol diet (HC; 12% fat and 1.5% cholesterol) for 2, 4, 8 or 12 weeks prior to tissue collection. Furthermore, to determine the effects of risk factor withdrawal, an additional group of swine received HC for 12 weeks and then CD for 8 weeks; a control group received HC continuously for 20 weeks. Endothelial cells were harvested from common carotid aorta. In parallel in vitro studies, cultured human aortic endothelial cells (HAEC) were treated with human LDL, GW3956 (LXR agonist) and RG108 (DNA methyltransferase [DNMT] inhibitor). In cells from both sources, DNA methylation at the NOS3 promoter was measured using methylation specific pyro sequencing, and endothelial gene expression was measured using RT PCR. Results: HC diet increased plasma cholesterol level from 75 mg/dl on CD to a plateau of about 540 mg/dl within 2 weeks. Endothelial NOS3 expression was significantly reduced (71±9 % of CD) after 4 weeks of HC, a level sustained at subsequent time points. Withdrawal of HC for 8 weeks did not recover NOS3 expression. After 12-week HC, the NOS3 promoter was hypermethylated. Withdrawal of HC did not reverse NOS3 promoter methylation. In vitro treatment of HAEC with human LDL (200 mg/dl total cholesterol) or GW3956 (5μM) suppressed NOS3 mRNA to 50% and 30% respectively, suggesting that LXR/RXR is involved in suppression of NOS3. Nitric oxide production was consistently suppressed by GW3959. Both could be reversed through inhibition of DNMTs by RG108. Conclusions: DNA methylation and LXR/RXR pathway can mediate the HC-suppression of endothelial NOS3. The study identifies novel pharmaceutical targets in treating endothelial dysfunction. Crosstalk between these pathways is under investigation.

scholarly journals Decreased Susceptibility of Glycated Very Low Density Lipoproteins to Lipoprotein Lipase in vitro and Prevention by Glutathione

1994 ◽  
Vol 1 (1) ◽  
pp. 8-14 ◽  
Author(s):  
Shuichi Saheki ◽  
Kohji Shishino ◽  
Yasuo Hitsumoto ◽  
Mitsuharu Murase ◽  
Nozomu Takeuchi ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Very Low Density Lipoproteins

scholarly journals Oxidized Low-Density Lipoprotein-Deteriorated Psoriasis Is Associated with the Upregulation of Lox-1 Receptor and Il-23 Expression In Vivo and In Vitro

2018 ◽  
Vol 19 (9) ◽  
pp. 2610 ◽  
Author(s):  
Chun-Ming Shih ◽  
Chien-Yu Huang ◽  
Kuo-Hsien Wang ◽  
Chun-Yao Huang ◽  
Po-Li Wei ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Cholesterol Diet ◽  
Low Density ◽  
Hacat Cells ◽  
Cholesterol Diet ◽  
Oxidized Low Density Lipoprotein ◽  
High Cholesterol ◽  
Tnf Α

Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of psoriasis and dyslipidemia is an important issue that may lead to the development of effective therapies. Under this principle, we investigated the influences of hyperlipidemia in imiquimod (IMQ)-induced psoriasis-like B6.129S2-Apoetm1Unc/J mice and oxidized low-density lipoprotein (oxLDL) in tumor necrosis factor (TNF)-α-stimulated Hacat cells. In our study, we showed that a high-cholesterol diet aggravated psoriasis-like phenomena in IMQ-treated B6.129S2-Apoetm1Unc/J mice. In vitro analysis showed that oxLDL increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. High-cholesterol diet aggravated IL-23 expression in IMQ-treated B6.129S2-Apoetm1Unc/J mice, and oxLDL induced IL-23 expression mediated by LOX-1 in TNF-α-stimulated Hacat cells. Therefore, it will be interesting to investigate the factors for the oxLDL induction of LOX-1 in psoriasis. LOX-1 receptor expression may be another novel treatment option for psoriasis and might represent the most promising strategy.

scholarly journals Lipoprotein lipase and hepatic lipase activities in a hypercholesterolaemic (RICO) strain of rat. Effect of dietary cholesterol

1990 ◽  
Vol 266 (2) ◽  
pp. 349-353 ◽  
Author(s):  
F Sultan ◽  
L E Cardona-Sanclemente ◽  
D Lagrange ◽  
C Lutton ◽  
S Griglio
Keyword(s):  
Lipoprotein Lipase ◽  
Hepatic Lipase ◽  
Control Diet ◽  
Dietary Cholesterol ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
Cholesterol Feeding ◽  
High Cholesterol ◽  
Rate Limiting

Hepatic lipase (HL) and lipoprotein lipase (LPL) were assayed in heparinized plasma from male normocholesterolaemic (SW) and genetically hypercholesterolaemic (RICO) rats. Both strains were fed on either a semi-purified control diet or the same diet enriched with 0.5% or 1% cholesterol. HL activity was similar in both groups of rats fed on the control diet. LPL activity was found to be significantly lower in RICO rats (35% decrease, P less than 0.05). Feeding with a high-cholesterol diet led to a decrease in HL activity (15-23%) in both groups of rats but no change was detected in LPL activity, which remained consistently lower in the RICO rats. Thus, with the control diet, LPL activity is lower in RICO rats but presumably is not rate-limiting for their triacylglycerol clearance, given the normal triacylglycerol levels present. After cholesterol feeding, however, the lower LPL activity may become rate-limiting together with the decrease in HL activity, as in these circumstances hypertriacylglycerolaemia was evident and the hypercholesterolaemia of this strain was further increased.

The catabolism of very low density lipoproteins

1985 ◽  
Vol 63 (8) ◽  
pp. 890-897 ◽  
Author(s):  
W. Carl Breckenridge
Keyword(s):  
Surface Composition ◽  
Hepatic Lipase ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Core Particle ◽  
Mechanism Of Formation ◽  
Very Low Density Lipoproteins ◽  
Apo E

The lipolysis of very low density lipoproteins (VLDL) in vitro is a useful model for the study of the process of conversion of this triacylglycerol rich lipoprotein into low (LDL) and high (HDL) density lipoproteins. Data is reviewed to show that a portion of surface cholesterol and phospholipid which becomes redundant during lipolysis is lost from the lipoprotein. In the absence of HDL, the material forms lipoprotein-X (LpX) like vesicles which are not readily disrupted by HDL once they are formed. In the presence of HDL during lipolysis, the material is largely incorporated into HDL. The data is used to suggest a mechanism of formation of LpX-like vesicles in conditions where the production of surface remnants exceeds the capacity of HDL to disrupt them. Evidence is also provided to show that apolipoproteins (apo) C-II, C-III, and E are lost from VLDL and that this loss is primarily in association with a neutral core particle of HDL size which can subsequently exchange lipids and apolipoproteins with plasma HDL. Such a mechanism could account for the removal of apo E and excess cholesteryl ester which is necessary for conversion of VLDL to LDL. The role of hepatic lipase in this process remains speculative. Recent evidence is reviewed and used to propose that the enzyme may serve to rearrange the neutral core and surface composition of LDL and HDL subfractions to allow for the packaging of cholesteryl esters and the cycling of apolipoproteins.

scholarly journals Hepatic lipase deficiency produces glucose intolerance, inflammation and hepatic steatosis

2015 ◽  
Vol 227 (3) ◽  
pp. 179-191 ◽  
Author(s):  
Irene Andrés-Blasco ◽  
Andrea Herrero-Cervera ◽  
Ángela Vinué ◽  
Sergio Martínez-Hervás ◽  
Laura Piqueras ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Glucose Intolerance ◽  
Hepatic Lipase ◽  
High Cholesterol Diet ◽  
Chow Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat ◽  
Obese People ◽  
Alcoholic Fatty Liver

Metabolic syndrome and type 2 diabetes mellitus constitute a major problem to global health, and their incidence is increasing at an alarming rate. Non-alcoholic fatty liver disease, which affects up to 90% of obese people and nearly 70% of the overweight, is commonly associated with MetS characteristics such as obesity, insulin resistance, hypertension and dyslipidemia. In the present study, we demonstrate that hepatic lipase (HL)-inactivation in mice fed with a high-fat, high-cholesterol diet produced dyslipidemia including hypercholesterolemia, hypertriglyceridemia and increased non-esterified fatty acid levels. These changes were accompanied by glucose intolerance, pancreatic and hepatic inflammation and steatosis. In addition, compared with WT mice, HL−/− mice exhibited enhanced circulating MCP1 levels, monocytosis and higher percentage of CD4+Th17+ cells. Consistent with increased inflammation, livers from HL−/− mice had augmented activation of the stress SAPK/JNK- and p38-pathways compared with the activation levels of the kinases in livers from WT mice. Analysis of HL−/− and WT mice fed regular chow diet showed dyslipidemia and glucose intolerance in HL−/− mice without any other changes in inflammation or hepatic steatosis. Altogether, these results indicate that dyslipidemia induced by HL-deficiency in combination with a high-fat, high-cholesterol diet promotes hepatic steatosis and inflammation in mice which are, at least in part, mediated by the activation of the stress SAPK/JNK- and p38-pathways. Future studies are warranted to asses the viability of therapeutic strategies based on the modulation of these kinases to reduce hepatic steatosis associated to lipase dysfunction.

Composition of very low density lipoproteins and in vitro effect of lipoprotein lipase

1991 ◽  
Vol 204 (1-3) ◽  
pp. 155-166 ◽  
Author(s):  
S. Saheki ◽  
I. Takahashi ◽  
M. Murase ◽  
N. Takeuchi ◽  
K. Uchida
Keyword(s):  
Lipoprotein Lipase ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Vitro Effect
Sign in / Sign up

Export Citation Format

Share Document