Leptin modulates ACAT1 expression and cholesterol efflux from human macrophages

2009 ◽  
Vol 297 (2) ◽  
pp. E474-E482 ◽  
Author(s):  
Shigeki Hongo ◽  
Takuya Watanabe ◽  
Shigeko Arita ◽  
Tomoko Kanome ◽  
Haruaki Kageyama ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Cholesterol Efflux ◽  
Leptin Receptor ◽  
Foam Cell ◽  
Cell Formation ◽  
Human Monocyte ◽  
Foam Cell Formation ◽  
Monocytic Differentiation ◽  
Macrophage Foam Cell ◽  
Cholesteryl Ester Accumulation

Leptin is an adipose tissue-derived hormone implicated in atherosclerosis and macrophage foam cell formation. The current study was conducted to examine the effect of leptin on cholesteryl ester accumulation in human monocytes/macrophages. Exogenously added leptin at 5 nM during differentiation of monocytes into macrophages for 7 days accelerated acetylated LDL (acetyl-LDL)-induced cholesteryl ester accumulation by 30–50%. Leptin did not affect endocytic uptake of acetyl-LDL; however, it increased ACAT activity 1.8-fold and ACAT-1 protein expression 1.9-fold. Among the four ACAT-1 mRNA transcripts, two shorter transcripts (2.8 and 3.6 kb) were upregulated ∼1.7-fold upon leptin treatment. The enhanced expression of ACAT-1 protein by leptin was suppressed by inhibitors of Janus-activated kinase2 (JAK2) and phosphatidylinositol 3-kinase (PI3K). HDL-mediated cholesterol efflux was suppressed by leptin, which was canceled by K-604, an ACAT-1 inhibitor. Expression of long form of leptin receptor was upregulated during monocytic differentiation into macrophages and sustained after differentiation. Thus, the results suggest that leptin accelerates cholesteryl ester accumulation in human monocyte-derived macrophages by increasing ACAT-1 expression via JAK2 and PI3K, thereby suppressing cholesterol efflux.

scholarly journals A Chlamydia pneumoniae Component That Induces Macrophage Foam Cell Formation Is Chlamydial Lipopolysaccharide

1998 ◽  
Vol 66 (11) ◽  
pp. 5067-5072 ◽  
Author(s):  
Murat V. Kalayoglu ◽  
Gerald I. Byrne
Keyword(s):  
Cholesteryl Ester ◽  
Chlamydia Pneumoniae ◽  
Elevated Temperatures ◽  
Foam Cell ◽  
Cell Formation ◽  
Disease Process ◽  
Foam Cell Formation ◽  
Human Macrophage ◽  
Macrophage Foam Cell ◽  
Cholesteryl Ester Accumulation

ABSTRACT Chlamydia pneumoniae infection is associated with atherosclerotic heart and vessel disease, but a causal relationship between this pathogen and the disease process has not been established. Recently, it was reported that C. pneumoniae induces human macrophage foam cell formation, a key event in early atheroma development, suggesting a role for the organism in atherogenesis. This study further examines C. pneumoniae-induced foam cell formation in the murine macrophage cell line RAW-264.7. Infected RAW cells accumulated cholesteryl esters when cultured in the presence of low-density lipoprotein in a manner similar to that described for human macrophages. Exposure of C. pneumoniae elementary bodies to periodate, but not elevated temperatures, inhibited cholesteryl ester accumulation, suggesting a role for chlamydial lipopolysaccharide (cLPS) in macrophage foam cell formation. Purified cLPS was found to be sufficient to induce cholesteryl ester accumulation and foam cell formation. Furthermore, the LPS antagonist lipid X inhibited C. pneumoniae and cLPS-induced lipid uptake. These data indicate that cLPS is a C. pneumoniae component that induces macrophage foam cell formation and suggest that infected macrophages chronically exposed to cLPS may accumulate excess cholesterol to contribute to atheroma development.

scholarly journals High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation

2012 ◽  
Vol 53 (10) ◽  
pp. 2081-2091 ◽  
Author(s):  
Jason M. Meyer ◽  
Ailing Ji ◽  
Lei Cai ◽  
Deneys R. van der Westhuyzen
Keyword(s):  
Cholesteryl Ester ◽  
Foam Cell ◽  
Cell Formation ◽  
High Capacity ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Selective Uptake

A reliable and reproducible assay for determining the effect of natural product on macrophages lipid uptake and cholesterol efflux: A case study of maslinic acid

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Bee Kee Ooi ◽  
Nafees Ahemad ◽  
Wei Hsum Yap
Keyword(s):  
Natural Product ◽  
Fluorescence Intensity ◽  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Lipid Uptake ◽  
Macrophage Foam Cell ◽  
Maslinic Acid

Macrophage foam cell formation represents a key feature that contributes to the development of atherosclerotic lesions. Assessment of cardioprotective natural compounds targeting macrophage foam cell formation processes including lipid uptake and cholesterol efflux could lead to the identification of potential lead compounds for development into novel anti-atherosclerotic drugs. In this case study, maslinic acid, a natural product was used to study the effect on lipid uptake and cholesterol efflux in THP-1-derived macrophages.  Oil red O (ORO) staining and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled oxidized low-density lipoprotein (Dil-labeled oxLDL) uptake assays were performed to determine lipid uptake by macrophages while cholesterol efflux was assessed using 3-hexanoyl-NBD labeled cholesterol. ORO-stained images were further analyzed using ImageJ analysis software to determine intracellular lipid droplets accumulation and flow cytometric analysis of mean fluorescence intensity were obtained to quantify Dil-labeled oxLDL uptake by macrophages. Meanwhile, 3-hexanoyl-NBD labeled cholesterol uptake and efflux from THP-1-derived macrophages were characterized. The fluorescence intensity values obtained from the medium and cell lysates were then converted into percentage of cholesterol efflux. The results have shown that incubation with maslinic acid suppressed oxLDL-induced macrophage foam cell formation which may be contributed from its effect in reducing lipid uptake and enhancing cholesterol efflux. In conclusion, the optimized ORO staining, Dil-labeled oxLDL uptake, and fluorescent-labeled cholesterol efflux assays provide reproducible and reliable results for assessment of foam cells formation.

scholarly journals SIRT 6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox‐ LDL condition

FEBS Journal ◽  
2017 ◽  
Vol 284 (9) ◽  
pp. 1324-1337 ◽  
Author(s):  
Jiangping He ◽  
Guangya Zhang ◽  
Qi Pang ◽  
Cong Yu ◽  
Jie Xiong ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell
Sign in / Sign up

Export Citation Format

Share Document