Resistin increases lipid accumulation by affecting class A scavenger receptor, CD36 and ATP-binding cassette transporter-A1 in macrophages

Tzong Shyuan Lee, Chun Yueh Lin, Jin Yi Tsai, Yuh Lin Wu, Kuo Hui Su, Kuo Yun Lu, Sheng Huang Hsiao, Ching Chian Pan, Yu Ru Kou, Yung Pei Hsu, Low Tone Ho*

*此作品的通信作者

研究成果: Article同行評審

63 引文 斯高帕斯(Scopus)

摘要

Aims: Resistin promotes macrophage-foam cell formation, but the mechanisms are unclear. In macrophages, lipid uptake is regulated by scavenger receptors (SR-A and CD36), while the cholesterol efflux is regulated by SR-BI, ATP-binding cassette transporter-A1 (ABCA1) and ABCG1. We investigated the mechanisms underlying the dysregulation by resistin of these regulators leading to promotion of lipid accumulation in bone marrow-derived macrophages. Main methods: Western blotting, real-time PCR and oil red O staining were performed. Key findings: Resistin exacerbated lipid accumulation in oxLDL-treated macrophages. Resistin treatment of oxLDL-untreated macrophages showed increased SR-A and CD36 mRNA and protein levels, and decreased ABCA1 protein level, while having no effect on SR-BI or ABCG1 expression. Up-regulation of SR-A and CD36 by resistin resulted from activation of AP-1 and PPARγ, respectively, and this was confirmed by the lack of activation of either after AP-1 inhibition using curcumin or SP600125, or PPARγ inhibition using GW9662, respectively. The down-regulation of ABCA1 by resistin was not accompanied by a reduced mRNA level or an activation of LXRα/RXR, but resulted from enhanced protein degradation as revealed by the abolition of the down-regulation after inhibition of the proteasome pathway using ALLN or MG-132. A combined inhibition by SP600125, GW9662 and ALLN prevented resistin-induced exacerbation of lipid accumulation in oxLDL-treated macrophages. Significance: Resistin promotes foam cell formation via dysregulation of SR-A, CD36 and ABCA1. SR-A and CD36 are transcriptionally up-regulated by resistin through AP-1 and PPARγ, respectively, whereas ABCA1 is down-regulated by resistin through proteasome-mediated enhancement of protein degradation.

原文English
頁(從 - 到)97-104
頁數8
期刊Life Sciences
84
發行號3-4
DOIs
出版狀態Published - 16 1月 2009

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