Abstract:
:Adiponectin, an adipocyte-derived protein, has antiatherogenic and antidiabetic effects, but how it confers the atherogenic effects is not well known. To study the antiatherogenic 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 the 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 the 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 extracellular signal-regulated kinas phosphorylation. In HCAECs, adiponectin inhibited oxLDL-induced endothelin-1 secretion and extracellular signal-regulated kinase 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 antiatherogenic 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
2020-11-21 00:00:00pages
100001eissn
0022-2275issn
1539-7262pii
S0022-2275(20)43629-6journal_volume
62pub_type
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journal_title:Journal of lipid research
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abstract::Several studies have documented the presence of Lp[a] in nonhuman primates. However, data are lacking in great apes such as the chimpanzee. We have studied the quantitative distribution of Lp[a], as well as the frequency of apo[a] phenotypes, in a population of chimpanzees living in Gabon. Monoclonal antibody 14A12, d...
journal_title:Journal of lipid research
pub_type: 杂志文章
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1983-12-01 00:00:00
abstract::Rats were fed either rat chow (control), chow + 20% olive oil (olive oil), or chow + 20% olive oil + 2% cholesterol (olive oil/cholesterol) as a single meal to study the short-term effects of fat and the above combination of fat/cholesterol-containing diets on plasma apoB concentration and its influence on the distrib...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1985-08-01 00:00:00
abstract::A synthetic analog of glucocerebroside, N-hexyl-O-glucosyl sphingosine, was found to inhibit the glucosidase in rat spleen that hydrolyzes glucocerebroside. At a concentration of 1 micro m, the analog inhibited the enzyme by 48%. The mode of action appeared to be competitive, probably aided by tight binding of the ami...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1973-03-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1194/jlr.M002972
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M600248-JLR200
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.D061499
更新日期:2015-09-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M060574
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1983-12-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M500203-JLR200
更新日期:2006-02-01 00:00:00
abstract::Rat spermatogenic cells contain sphingomyelins (SMs) and ceramides (Cers) with very long-chain PUFAs (VLCPUFAs) in nonhydroxylated (n-V) and 2-hydroxylated (h-V) forms. How these atypical species distribute among membrane fractions during differentiation was investigated here using a detergent-free procedure to isolat...
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pub_type: 杂志文章
doi:10.1194/jlr.M072595
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journal_title:Journal of lipid research
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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:1994-01-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
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doi:10.1194/jlr.M021030
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Synthesis of apolipoprotein (apo)E in hepatocytes leads to both secretion and retention in cell surface pools. Inclusion of Brefeldin A to HepG2 cells prompted a rapid decrease of cell surface apoE to about 37% of control values after a 3-h incubation. The t(1/2) for this dynamic pool was estimated to be 15 min. In co...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2001-09-01 00:00:00
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journal_title:Journal of lipid research
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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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journal_title:Journal of lipid research
pub_type: 杂志文章
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