| RRC ID |
44471
|
| Author |
Nakaya K, Ayaori M, Uto-Kondo H, Sotherden GM, Nishida T, Katamoto H, Miura Y, Takiguchi S, Yakushiji E, Iizuka M, Ogura M, Sasaki M, Yogo M, Komatsu T, Adachi T, Maruyama C, Ikewaki K.
|
| Title |
Overexpression of stearoyl-coenzyme A desaturase 1 in macrophages promotes reverse cholesterol transport.
|
| Journal |
Biochim Biophys Acta
|
| Abstract |
Stearoyl-coenzyme A desaturase 1 (SCD1) is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. However, the impact of SCD1 on atherosclerosis remains unclear. The aim of this study was to determine whether SCD1 affects macrophage reverse cholesterol transport (RCT) in mice. Compared to the control, adenoviral-mediated SCD1 overexpression in RAW264.7 macrophages increased cholesterol efflux to HDL, but not to apoA-I, without clear changes in ABCA1, ABCG1 and SR-BI expressions. While knockdown of ABCG1 and SR-BI did not affect the SCD1-induced cholesterol efflux to HDL, SCD1-overexpressing macrophages promoted the formation of both normal- and large-sized HDL in media, accompanying increased apolipoprotein A-I levels in HDL fractions. Transformation to larger particles of HDL was independently confirmed by nuclear magnetic resonance-based lipoprotein analysis. Interestingly, media transfer assays revealed that HDL generated by SCD1 had enhanced cholesterol efflux potential, indicating that SCD1 transformed HDL to a more anti-atherogenic phenotype. To study macrophage RCT in vivo, (3)H-cholesterol-labeled RAW264.7 cells overexpressing SCD1 or the control were intraperitoneally injected into mice. Supporting the in vitro data, injection of SCD1-macrophages resulted in significant increases in (3)H-tracer in plasma, liver, and feces compared to the control. Moreover, there was a shift towards larger particles in the (3)H-tracer distribution of HDL fractions obtained from the mice. In conclusion, macrophage-specific SCD1 overexpression promotes overall RCT through increased cholesterol efflux to HDL, suggesting that macrophage SCD1 achieves an anti-atherogenic effect by enhancing RCT.
|
| Volume |
1831(8)
|
| Pages |
1402-11
|
| Published |
2013-8-1
|
| DOI |
10.1016/j.bbalip.2013.05.009
|
| PII |
S1388-1981(13)00123-6
|
| PMID |
23747827
|
| MeSH |
ATP Binding Cassette Transporter 1
ATP Binding Cassette Transporter, Subfamily G, Member 1
ATP-Binding Cassette Transporters / genetics
ATP-Binding Cassette Transporters / metabolism
Animals
Atherosclerosis / enzymology
Atherosclerosis / genetics
Atherosclerosis / pathology
Atherosclerosis / therapy
Biological Transport, Active / genetics
Cell Line
Cholesterol / genetics
Cholesterol / metabolism*
Gene Expression Regulation, Enzymologic*
Humans
Lipoproteins / genetics
Lipoproteins / metabolism
Lipoproteins, HDL / genetics
Lipoproteins, HDL / metabolism*
Macrophages / enzymology*
Macrophages / pathology
Mice
Stearoyl-CoA Desaturase / biosynthesis*
Stearoyl-CoA Desaturase / genetics
|
| IF |
3.411
|
| Times Cited |
10
|
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
RAW 264(RCB0535) |
