Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver.
Plasma high density lipoprotein (HDL)-cholesterol levels are negatively correlated with the incidence of coronary artery disease. HDL plays an important role in protecting against atherosclerosis by removing cholesterol from atheroma and transporting it back to the liver. The ATP-binding cassette transporters (ABCA1 and ABCG1) and scavenger receptor BI (SR-BI) are thought to be one of the rate-limiting factors to generate HDL in the liver. Adiponectin (APN) secreted from adipocytes is also one of the important molecules to inhibit the development of atherosclerosis. Recently, it has been reported that plasma HDL-cholesterol levels are positively correlated with plasma APN concentrations in humans. Therefore, we investigated the association of APN with HDL assembly in the liver. Human hepatoma cell line, HepG2 cells, were incubated for 24h in the culture medium with the indicated concentrations of recombinant APN. APN enhanced the mRNA level of apolipoprotein A-I (apoA-I) in HepG2 cells and increased the secretion of apoA-I from the cells to the medium. Furthermore, APN increased both mRNA and protein levels of ABCA1, but not ABCG1 and SR-BI, in HepG2 cells. Taken together, the current study demonstrates that APN might protect against atherosclerosis by increasing HDL assembly through enhancing ABCA1 pathway and apoA-1 synthesis in the liver.
Matsuura
Fumihiko
F
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. fumihiko@imed2.med.osaka-u.ac.jp
Oku
Hiroyuki
H
Koseki
Masahiro
M
Sandoval
Jose C
JC
Yuasa-Kawase
Miyako
M
Tsubakio-Yamamoto
Kazumi
K
Masuda
Daisaku
D
Maeda
Norikazu
N
Tsujii
Ken-ichi
K
Ishigami
Masato
M
Nishida
Makoto
M
Hirano
Ken-ichi
K
Kihara
Shinji
S
Hori
Masatsugu
M
Shimomura
Iichiro
I
Yamashita
Shizuya
S
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D052242:Adiponectin / Q000008:administration & dosage*; D016632:Apolipoprotein A-I / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D052242:Adiponectin; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D002784:Cholesterol