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.
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)