Critical role of leukotriene B4 receptor signaling in mouse 3T3-L1 preadipocyte differentiation.

Critical role of leukotriene B4 receptor signaling in mouse 3T3-L1 preadipocyte differentiation.
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DOI:
10.1186/1476-511x-12-122
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发表时间:
2013-08-09
影响因子:
4.5
通讯作者:
Kamisaki Y
Kamisaki Y
中科院分区:
医学3区
文献类型:
--
作者:
Hirata K;Wada K;Murata Y;Nakajima A;Yamashiro T;Kamisaki Y

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肥胖相关的多种炎症介质可能与胰岛素抵抗密切相关。白三烯(LT)参与炎症反应。然而,关于LT在脂肪细胞分化中的作用的报道很少。因此,我们研究了白三烯B4(LTB 4)-白三烯受体(BLT)信号在小鼠3 T3-L1成纤维前脂肪细胞分化为成熟脂肪细胞中的作用。用脂氧合酶(LOX)抑制剂、BLT拮抗剂和针对BLT 1和BLT 2的小干扰RNA(siRNA)处理小鼠3 T3-L1前脂肪细胞,以阻断LTB 4-BLT信号通路,然后评价脂肪细胞分化,如脂质积累和甘油三酯增加。通过用LOX抑制剂或BLT拮抗剂处理阻断BLT信号传导抑制前脂肪细胞分化成成熟脂肪细胞。此外,通过siRNA敲低BLT 1和BLT 2显著抑制分化。这些结果表明,LTB 4-BLT信号通路可能正调控前脂肪细胞分化,并成为控制脂肪细胞分化的限速系统。LTB 4-BLT信号通路提供了一个有效的调节信号,加速小鼠3 T3-L1前脂肪细胞的分化。需要进一步研究以确认LTB 4和BLT信号通路在前脂肪细胞分化中的确切作用。
Various inflammatory mediators related to obesity might be closely related to insulin resistance. Leukotrienes (LTs) are involved in inflammatory reactions. However, there are few reports regarding the role of LTs in adipocyte differentiation. Therefore, we investigated the role of leukotriene B4 (LTB4)-leukotriene receptor (BLT) signaling in mouse 3T3-L1 fibroblastic preadipocyte differentiation to mature adipocytes. Mouse 3T3-L1 preadipocytes were treated with lipoxygenase (LOX) inhibitors, BLT antagonist, and small interfering RNA (siRNA) for BLT1 and BLT2 to block the LTB4-BLT signaling pathway, then the adipocyte differentiation such as lipid accumulation and the increase in triglyceride was evaluated. Blockade of BLT signaling by treatment with a LOX inhibitor or a BLT antagonist suppressed preadipocyte differentiation into mature adipocytes. In addition, knockdown of BLT1 and BLT2 by siRNAs dramatically inhibited differentiation. These results indicate the LTB4-BLT signaling pathway may positively regulate preadipocyte differentiation and be a rate-limiting system to control adipocyte differentiation. The LTB4-BLT signaling pathway provides a potent regulatory signal that accelerates the differentiation of mouse 3T3-L1 preadipocytes. Further investigations are necessary to confirm the exact role of LTB4 and BLTs signaling pathways in preadipocyte differentiation.