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Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2242-8. doi: 10.1161/ATVBAHA.110.210427. Epub 2010 Sep 9.

Apolipoprotein CIII induces monocyte chemoattractant protein-1 and interleukin 6 expression via Toll-like receptor 2 pathway in mouse adipocytes.

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1
Department of Geriatrics and Vascular Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 1138519, Japan.

Abstract

OBJECTIVE:

To examine the direct effect of apolipoprotein CIII (apoCIII) on adipokine expressions that are involved in obesity, insulin resistance, or metabolic syndrome.

METHODS AND RESULTS:

ApoCIII in triglyceride-rich lipoproteins is elevated in patients with obesity, insulin resistance, or metabolic syndrome. Its level is also associated with proinflammatory adipokines. Fully differentiated mouse 3T3L1 adipocytes were incubated with apoCIII. ApoCIII activated nuclear factor κB of 3T3L1 adipocytes and induced the expression of monocyte chemoattractant protein (MCP) 1 and interleukin (IL) 6. ApoCIII also activated extracellular signal-regulated kinase and p38. Mitogen-activated protein kinase kinase (MEK)-1 inhibitor PD98059, but not p38 inhibitor SB203580, inhibited apoCIII-induced upregulation of MCP-1 and IL-6. Previously, it was shown that apoCIII activates proinflammatory signals through toll-like receptor (TLR) 2. TLR2-blocking antibody abolished activation of nuclear factor κB and extracellular signal-regulated kinase induced by apoCIII and inhibited apoCIII-induced upregulation of MCP-1 and IL-6. ApoCIII also reduced adiponectin expression of 3T3L1 adipocytes, which was recovered by TLR2-blocking antibody. ApoCIII induced the expression of MCP-1 and IL-6 in TLR2-overexpressed human embryonic kidney 293 cells but not wild-type human embryonic kidney 293 cells without TLR2. ApoCIII induced the expression of MCP-1 and IL-6 and decreased adiponectin expression in white adipose tissue of wild-type mice but not of TLR2-deficient mice in vivo.

CONCLUSIONS:

ApoCIII may activate extracellular signal-regulated kinase and nuclear factor kB through TLR2 and induce proinflammatory adipokine expression in vitro and in vivo. Thus, apoCIII links dyslipidemia to inflammation in adipocytes, which, in turn, may contribute to atherosclerosis.

PMID:
20829510
PMCID:
PMC3203842
DOI:
10.1161/ATVBAHA.110.210427
[Indexed for MEDLINE]
Free PMC Article
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