Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan.
Lipids Health Dis. 2013 Aug 9;12:122. doi: 10.1186/1476-511X-12-122.
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.
与肥胖相关的各种炎症介质可能与胰岛素抵抗密切相关。白三烯(LTs)参与炎症反应。然而,关于 LTs 在脂肪细胞分化中的作用的报道很少。因此,我们研究了白细胞三烯 B4(LTB4)-白细胞三烯受体(BLT)信号在小鼠 3T3-L1 成纤维前体细胞向成熟脂肪细胞分化中的作用。
用脂氧合酶(LOX)抑制剂、BLT 拮抗剂和 BLT1 和 BLT2 的小干扰 RNA(siRNA)处理小鼠 3T3-L1 前体细胞,阻断 LTB4-BLT 信号通路,然后评估脂肪细胞分化,如脂滴积累和甘油三酯增加。
用 LOX 抑制剂或 BLT 拮抗剂阻断 BLT 信号可抑制前体细胞向成熟脂肪细胞分化。此外,siRNA 敲低 BLT1 和 BLT2 可显著抑制分化。这些结果表明,LTB4-BLT 信号通路可能正向调节前体脂肪细胞分化,并成为控制脂肪细胞分化的限速系统。
LTB4-BLT 信号通路提供了一个有效的调节信号,加速了小鼠 3T3-L1 前体脂肪细胞的分化。需要进一步的研究来确认 LTB4 和 BLT 信号通路在脂肪细胞分化中的确切作用。