Adiponectin down-regulates acyl-coenzyme A:cholesterol acyltransferase-1 in cultured human monocyte-derived macrophages.
Acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) catalyzes the formation of cholesteryl esters (CE) and plays a significant role in formation of macrophage-derived foam cells in atherosclerotic lesions. Adiponectin was reported to play an anti-atherogenic role by inhibiting class A scavenger receptor (SR-A) expression in human macrophages. To further clarify its additional property, we examined its effect on ACAT-1 expression using human macrophages. Immunoblot analyses revealed a significant reduction of ACAT-1 protein by a low concentration (1 microg/ml) of adiponectin. The ACAT activity was also decreased in parallel by adiponectin. Northern blot analyses revealed that all four ACAT-1 mRNA transcripts (2.8, 3.6, 4.3, and 7.0 kb) were decreased almost equally by adiponectin. Furthermore, acetyl-LDL-induced CE-accumulation in these macrophages was reduced significantly by this adipocytokine. These results demonstrate the inhibitory effect of adiponectin on ACAT-1 expression, suggesting that adiponectin may play an anti-atherogenic role by down-regulating the expression of ACAT-1 as well as SR-A in human macrophages.
Furukawa
Kohichiro
K
Department of Medical Biochemistry, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Hori
Masaharu
M
Ouchi
Noriyuki
N
Kihara
Shinji
S
Funahashi
Tohru
T
Matsuzawa
Yuji
Y
Miyazaki
Akira
A
Nakayama
Hitoshi
H
Horiuchi
Seikoh
S
D052242:Adiponectin; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008264:Macrophages / Q000201:enzymology*; D009000:Monocytes / Q000201:enzymology*; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D002785:Sterol O-Acyltransferase / Q000235:genetics / Q000502:physiology*
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D002785:Sterol O-Acyltransferase