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脂联素通过增加肝脏中高密度脂蛋白的组装来加速胆固醇逆向转运。

Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver.

作者信息

Matsuura Fumihiko, Oku Hiroyuki, Koseki Masahiro, Sandoval Jose C, Yuasa-Kawase Miyako, Tsubakio-Yamamoto Kazumi, Masuda Daisaku, Maeda Norikazu, Tsujii Ken-ichi, Ishigami Masato, Nishida Makoto, Hirano Ken-ichi, Kihara Shinji, Hori Masatsugu, Shimomura Iichiro, Yamashita Shizuya

机构信息

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.

出版信息

Biochem Biophys Res Commun. 2007 Jul 13;358(4):1091-5. doi: 10.1016/j.bbrc.2007.05.040. Epub 2007 May 15.

Abstract

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.

摘要

血浆高密度脂蛋白(HDL)胆固醇水平与冠状动脉疾病的发病率呈负相关。HDL通过从动脉粥样硬化斑块中清除胆固醇并将其转运回肝脏,在预防动脉粥样硬化中发挥重要作用。ATP结合盒转运蛋白(ABCA1和ABCG1)以及清道夫受体BI(SR-BI)被认为是肝脏中生成HDL的限速因素之一。脂肪细胞分泌的脂联素(APN)也是抑制动脉粥样硬化发展的重要分子之一。最近,有报道称在人类中血浆HDL胆固醇水平与血浆APN浓度呈正相关。因此,我们研究了APN与肝脏中HDL组装的关联。将人肝癌细胞系HepG2细胞在含有指定浓度重组APN的培养基中孵育24小时。APN提高了HepG2细胞中载脂蛋白A-I(apoA-I)的mRNA水平,并增加了apoA-I从细胞向培养基中的分泌。此外,APN增加了HepG2细胞中ABCA1的mRNA和蛋白水平,但未增加ABCG1和SR-BI的水平。综上所述,当前研究表明,APN可能通过增强肝脏中的ABCA1途径和apoA-1合成来增加HDL组装,从而预防动脉粥样硬化。

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