Cholesterol metabolism in human monocyte-derived macrophages: Stimulation of cholesteryl ester formation and cholesterol excretion by serum lipoproteins

Lipids ◽  
1982 ◽  
Vol 17 (10) ◽  
pp. 709-715 ◽  
Author(s):  
Daniel H. Albert ◽  
Maret G. Traber ◽  
Herbert J. Kayden
Keyword(s):  
Cholesteryl Ester ◽  
Cholesterol Metabolism ◽  
Human Monocyte ◽  
Serum Lipoproteins ◽  
Ester Formation ◽  
Cholesterol Excretion ◽  
Stimulation Of

Lipid synthesis in macrophages derived from the human cell line THP-1: modulation of the effects of native and oxidized chylomicron-remnant-like particles by oestrogen

2001 ◽  
Vol 101 (4) ◽  
pp. 403-413 ◽  
Author(s):  
Mariarosaria NAPOLITANO ◽  
Kelly V. BATT ◽  
Michael AVELLA ◽  
Elena BRAVO ◽  
Kathleen M. BOTHAM
Keyword(s):  
Cholesteryl Ester ◽  
Cell Line ◽  
Lipid Synthesis ◽  
Thiobarbituric Acid ◽  
Human Monocyte ◽  
Cholesterol Esterification ◽  
Chylomicron Remnant ◽  
Triacylglycerol Synthesis ◽  
Ester Formation ◽  
Chylomicron Remnants

The effects of native and oxidized chylomicron remnants on the synthesis of cholesteryl ester and triacylglycerol in macrophages, and the way that this is influenced by exposure of the cells to oestrogen, was investigated using the human monocyte cell line THP-1 and chylomicron-remnant-like particles containing human apolipoprotein E (CRLPs). Synthesis of the lipids was measured by the incorporation of [3H]oleate into cholesteryl ester and triacylglycerol. CRLPs (5-40μg of cholesterol/ml) containing either trilinolein or triolein as the triacylglycerol component caused a dose-dependent decrease in cholesteryl ester formation, while triacylglycerol production was unchanged. After oxidation of the CRLPs, the level of thiobarbituric acid-reactive substances was increased by 6.3-fold and 2.2-fold in particles containing trilinolein and triolein respectively. Furthermore, CRLPs containing oxidized trilinolein lost their ability to down-regulate cholesterol esterification, while CRLPs containing oxidized triolein did not. Both types of oxidized CRLPs decreased triacylglycerol synthesis. Treatment of the macrophages with 17β-oestradiol caused increases of approx. 94% and 34% in the synthesis of cholesteryl ester and triacylglycerol respectively in the absence of CRLPs. The differences between control and oestrogen-treated cells were abolished, however, when CRLPs (40μg of cholesterol/ml) were added to the incubations. In addition, in contrast with their lack of effect in control cells, CRLPs containing oxidized trilinolein decreased cholesterol esterification in oestrogen-treated cells by approx. 48%. These findings with CRLPs suggest that chylomicron remnants have significant effects on cholesteryl ester and triacylglycerol synthesis in macrophages, which may be modulated both by the oxidation state of the particles and by oestrogen.

scholarly journals Polyphenol-Rich Black Elderberry Extract Stimulates Transintestinal Cholesterol Excretion

2021 ◽  
Vol 11 (6) ◽  
pp. 2790
Author(s):  
Sohyeon Jeon ◽  
Minji Kim ◽  
Bohkyung Kim
Keyword(s):  
Messenger Rna ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Mrna Levels ◽  
Expression Of Genes ◽  
Apical Side ◽  
Cholesterol Excretion ◽  
Stimulation Of

Hypercholesterolemia is the primary risk factor for cardiovascular disease (CVD). Recent studies reported that the stimulation of transintestinal cholesterol excretion (TICE), a nonbiliary cholesterol excretion, can be a strategy for preventing CVD. Black elderberry (Sambucus nigra) has been reported to reduce the risk of CVD via its antioxidant, anti-inflammatory, and hypocholesterolemic effects. However, little is known about the role of black elderberry in intestinal cholesterol metabolism despite its well-known effects on cholesterol homeostasis regulation. To investigate the effects of polyphenol-rich black elderberry extract (BEE) on intestinal cholesterol metabolism, we measured the expression of genes involved in cholesterol biosynthesis and flux in Caco-2 cells. BEE significantly decreased the messenger RNA (mRNA) and protein levels of genes for cholesterol absorption, such as Niemann–Pick C1 Like 1 and ATP-binding cassette transporter A1 (ABCA1). In contrast, there was marked induction of low-density lipoprotein receptor, ABCG5/G8, and ABCB1 in BEE-treated Caco-2 cells. Furthermore, BEE decreased the expression of genes for lipogenesis and altered the mRNA levels of sirtuins. All of the genes altered by BEE were in the direction of flux cholesterol from the basolateral to apical side of enterocytes, indicating stimulation of TICE. These results support the hypocholesterolemic effects of BEE for the prevention of CVD.

scholarly journals Stimulation of Cholesterol Excretion by the Liver X Receptor Agonist Requires ATP-binding Cassette Transporters G5 and G8

2003 ◽  
Vol 278 (18) ◽  
pp. 15565-15570 ◽  
Author(s):  
Liqing Yu ◽  
Jennifer York ◽  
Klaus von Bergmann ◽  
Dieter Lutjohann ◽  
Jonathan C. Cohen ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Liver X Receptor ◽  
Atp Binding ◽  
Atp Binding Cassette Transporters ◽  
Cholesterol Excretion ◽  
Liver X Receptor Agonist ◽  
Stimulation Of ◽  
Atp Binding Cassette

Cholesterol Metabolism and Vitamin B6. III. The Stimulation of Hepatic Cholesterogenesis in the Vitamin B6-Deficient Rat

1971 ◽  
Vol 49 (8) ◽  
pp. 933-935 ◽  
Author(s):  
C. M. Hinse ◽  
P. J. Lupien
Keyword(s):  
Vitamin B6 ◽  
Cholesterol Metabolism ◽  
Krebs Cycle ◽  
Pool Size ◽  
Liver Slices ◽  
Liver Homogenates ◽  
The Difference ◽  
Hepatic Cholesterogenesis ◽  
Stimulation Of

The rate of incorporation of labeled acetate into cholesterol by liver slices of pyridoxine-deficient rats was found to be three times that of control rats; with liver homogenates the difference between the two groups was even greater. Using the CO2 trapping technique, a 30% decrease in the hepatic acetate pool size was observed in pyridoxine-deficient rats and a 20% increase in pair-fed rats. Activity of the Krebs cycle was decreased by a third in the pair-fed rats.

scholarly journals Genotyping of 2 Cholesteryl Ester Transfer Protein Gene Variants Among Coronary Artery Disease Patients

2020 ◽  
Vol 5 (3) ◽  
pp. 96-100
Author(s):  
Saeid Morovvati ◽  
Nima Kazemi Koohbanani ◽  
Iman Salahshouri Far ◽  
Fatemeh Karami
Keyword(s):  
Coronary Artery ◽  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Protein Function ◽  
Cholesterol Metabolism ◽  
Density Lipoprotein ◽  
Transfer Protein ◽  
Polymerase Chain ◽  
Artery Disease

Introduction: Coronary artery diseases (CAD) are still among the top causes of death in most populations. The polymorphisms of the cholesteryl ester transfer protein (CETP) gene can influence the risk of CAD through modulating cholesterol metabolism. In this regard, the current study aimed to determine the role of the 2 important CETP gene polymorphisms in CAD patients. Methods: To this end, DNA was extracted from the whole blood of 100 CAD patients and 100 healthy controls and then subjected to polymerase chain reaction-restriction fragment length polymorphism for the genotyping of rs5882 and rs708272 polymorphisms.Results: Based on the results, no meaningful association was found between rs5882 and rs708272 polymorphisms, neither separately nor in combination, and the risk of CAD. However, the risk of CAD significantly increased in male rs5882 polymorphism carriers (P = 0.01). Finally, no significant association was demonstrated between serum high-density lipoprotein levels and the genotypes or alleles of neither rs5882 nor rs708272 polymorphism. Conclusion: Despite the finding regarding the lack of an association between CAD and the studied polymorphisms of the CETP gene, the importance of those variants in CETP protein function and CAD pathogenesis warrants further investigation on larger populations.

Abstract 651: Autophagic Cholesterol Metabolism in Macrophages with Lysosome Dysfunction

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Courtney Netherland-Van Dyke ◽  
Carrie E Romer ◽  
W G Jerome
Keyword(s):  
Cholesteryl Ester ◽  
Cholesterol Metabolism ◽  
Foam Cell ◽  
Sterol Metabolism ◽  
Human Macrophages ◽  
Lysosomal Dysfunction ◽  
The Face ◽  
Macrophage Dysfunction ◽  
Important Pathway ◽  
In Cells

Extensive cholesterol accumulation in human macrophages inhibits lysosome function; a key attribute of many late-stage atherosclerosis foam cells. Lipophagy (a specialized form of autophagy) delivers lipids, like cholesteryl esters, to lysosomes where the esters are hydrolyzed to unesterified cholesterol which can be utilized in membranes or effluxed from the cell. Lipophagy has been shown to be an important pathway in foam cell sterol metabolism. We investigated what occurs to lipophagy when lysosome function is disrupted by excess cholesterol. Does autophagy continue? Does autophagy transport lipid to non-functioning lysosomes and thus contribute to overall lysosomal dysfunction and lysosomal sterol accumulation? In macrophages with dysfunctional lysosomes, how does inhibition of autophagy effect overall sterol balance and macrophage function?. We incubated human macrophages with aggregated LDL to produce macrophages with various degrees of lysosome dysfunction (confirmed by lysosome pH measurement and cholesteryl ester hydrolysis). To assess the role of lipophagy in changes in cellular sterol metabolism, we compared lipid metabolism as lysosomes became more dysfunctional and also with identical cells in which autophagy was inhibited with vinblastin. Increases in lysosome dysfunction did not alter the constitutive rate of autophagy as measured by proteins critical to autophagosome assembly (Atg7, Atg5, p62, LC3) and visualization of autophagosomes. Moreover, autophagy targeted lipid droplet material to lysosomes as indicated by the progressive accumulation of perilipin 2 in lysosomes and a significant decrease in lysosome cholesteryl ester content when autophagy was inhibited. In cells with normal functioning lysosomes, inhibition of autophagy increased total cell sterol levels. However, in cells where lysosomal dysfunction was prominent, lysosomal levels of sterol decreased and efflux of cholesterol was slightly enhanced when autophagy was inhibited. Our data indicates that lipophagy continues in the face of lysosome dysfunction and autophagy-delivered cholesteryl ester can exacerbate overall lysosome sterol accumulation and macrophage dysfunction when foam cell sterol is excessive.

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