RRC ID |
45332
|
著者 |
Hamada Y, Nagasaki H, Fujiya A, Seino Y, Shang QL, Suzuki T, Hashimoto H, Oiso Y.
|
タイトル |
Involvement of de novo ceramide synthesis in pro-inflammatory adipokine secretion and adipocyte-macrophage interaction.
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ジャーナル |
J Nutr Biochem
|
Abstract |
Interaction between adipocytes and macrophages has been suggested to play a central role in the pathogenesis of obesity. Ceramide, a sphingolipid de novo synthesized from palmitate, is known to stimulate pro-inflammatory cytokine secretion from multiple types of cells. To clarify whether de novo synthesized ceramide contributes to cytokine dysregulation in adipocytes and macrophages, we observed cytokine secretion in mature 3T3-L1 adipocytes (L1) and RAW264.7 macrophages (RAW) cultured alone or co-cultured under the suppression of de novo ceramide synthesis. Palmitate enhanced ceramide accumulation and stimulated the expression and secretion of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in L1. The suppression of serine-palmitoyl transferase, a rate-limiting enzyme of de novo ceramide synthesis, by myriocin or siRNA attenuated those palmitate-induced alterations, and a ceramide synthase inhibitor fumonisin B1 showed similar results. In contrast, the inhibitor of sphingosine kinase or a membrane-permeable ceramide analogue augmented the cytokine secretion. Myriocin effects on the palmitate-induced changes were not abrogated by toll-like receptor-4 blockade. Although palmitate stimulated RAW to secrete tumor necrosis factor-α (TNF-α), it did not significantly increase ceramide content, and neither myriocin nor fumonisin B1 attenuated the TNF-α hypersecretion. The co-culture of L1 with RAW markedly augmented IL-6 and MCP-1 levels in media. Myriocin or fumonisin B1 significantly lowered these cytokine levels and suppressed the gene expression of TNF-α and MCP-1 in RAW and of IL-6 and MCP-1 in L1. In conclusion, de novo synthesized ceramide partially mediates the palmitate effects on pro-inflammatory adipokines and is possibly involved in the interaction with macrophages.
|
巻・号 |
25(12)
|
ページ |
1309-16
|
公開日 |
2014-12-1
|
DOI |
10.1016/j.jnutbio.2014.07.008
|
PII |
S0955-2863(14)00172-7
|
PMID |
25283329
|
MeSH |
3T3-L1 Cells
Adipocytes / metabolism*
Adipokines / metabolism*
Animals
Cell Line, Tumor
Ceramides / biosynthesis*
Chemokine CCL2 / genetics
Chemokine CCL2 / metabolism
Coculture Techniques
Fatty Acids, Monounsaturated / pharmacology
Fumonisins / pharmacology
Interleukin-6 / genetics
Interleukin-6 / metabolism
Macrophages / metabolism*
Mice
Palmitates / pharmacology
RNA, Messenger / genetics
RNA, Messenger / metabolism
Serine C-Palmitoyltransferase / metabolism
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / metabolism
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism
|
IF |
4.873
|
引用数 |
18
|
WOS 分野
|
NUTRITION & DIETETICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
RAW 264(RCB0535) |