Abstract:
:Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL's atherogenicity. L5, the most electronegative subfraction of LDL, induces atherogenic responses similarly to copper-oxidized LDL (oxLDL). Unlike native LDL endocytosed via the LDL receptor, L5 and oxLDL are internalized by cells via the lectin-like oxidized LDL receptor-1 (LOX-1). Using enzyme-linked immunosorbent assays (ELISAs), we showed that adiponectin preferentially bound oxLDL but not native LDL. In Chinese hamster ovary (CHO) cells transfected with LOX-1 or LDL receptor, adiponectin selectively inhibited the uptake of oxLDL but not of native LDL, respectively. Furthermore, adiponectin suppressed the internalization of oxLDL in human coronary artery endothelial cells (HCAECs) and THP-1-derived macrophages. Western blot analysis of human plasma showed that adiponectin was abundant in L5 but not in L1, the least electronegative subfraction of LDL. Sandwich ELISAs with anti-adiponectin and anti-apolipoprotein B antibodies confirmed the binding of adiponectin to L5 and oxLDL. In LOX-1-expressing CHO cells, adiponectin inhibited cellular responses to oxLDL and L5, including nuclear factor-κB activation and ERK phosphorylation. In HCAECs, adiponectin inhibited oxLDL-induced endothelin-1 secretion and ERK phosphorylation. Conversely, oxLDL suppressed the adiponectin-induced activation of adenosine monophosphate-activated protein kinase in COS-7 cells expressing adiponectin receptor AdipoR1. Our findings suggest that adiponectin binds and inactivates atherogenic LDL, providing novel insight into the anti-atherogenic mechanisms of adiponectin.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Kakino A,Fujita Y,Ke LY,Chan HC,Tsai MH,Dai CY,Chen CH,Sawamura Tdoi
10.1194/jlr.RA120000767subject
Has Abstractpub_date
2020-11-03 00:00:00eissn
0022-2275issn
1539-7262pii
jlr.RA120000767pub_type
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:1996-02-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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更新日期:2002-08-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:1987-10-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1982-07-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1970-09-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
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更新日期:2016-03-01 00:00:00
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
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journal_title:Journal of lipid research
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更新日期:2000-07-01 00:00:00
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journal_title:Journal of lipid research
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更新日期:1968-05-01 00:00:00
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