EPA blocks TNF-α-induced inhibition of sugar uptake in Caco-2 cells via GPR120 and AMPK
EPA blocks TNF-α-induced inhibition of sugar uptake in Caco-2 cells via GPR120 and AMPK
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DOI：
10.1002/jcp.26115
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发表时间：
2018-03-01
影响因子：
5.6
通讯作者：
Pilar Lostao, Maria
中科院分区：
文献类型：
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作者：
Castilla-Madrigal, Rosa;Barrenetxe, Jaione;Pilar Lostao, Maria
本工作的目的是在Caco-2细胞中研究二十碳五烯酸（EPA）（一种欧米茄-3多不饱和脂肪酸）是否可以阻断肿瘤坏死因子-α（TNF-alpha）对糖转运的抑制作用，并确定相关的细胞内信号通路。Caco-2细胞与TNF-α和EPA预孵育1 h后，EPA阻止了细胞因子对α-甲基-D-葡萄糖（α MG）摄取（15 min）和刷状缘膜SGLT 1表达的抑制作用（通过Western blot测定）。ERK 1/2抑制剂PD 98059和AMPK激活剂AICAR也阻止了TNF-α对α MG摄取和SGLT 1表达的抑制作用。有趣的是，AMPK抑制剂化合物C消除了EPA阻止TNF-α诱导的糖摄取和转运蛋白表达减少的能力。GPR 120拮抗剂AH 7614也阻断EPA对TNF-α诱导的α MG摄取和AMPK磷酸化减少的预防作用。总之，TNF-α通过激活ERK 1/2途径降低刷状缘膜中SGLT 1的表达，从而抑制α MG摄取。EPA通过参与GPR 120和AMPK活化来阻止TNF-α的抑制作用。
The aim of the present work was to investigate in Caco-2 cells whether eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, could block the inhibitory effect of tumor necrosis factor-alpha (TNF-alpha) on sugar transport, and identify the intracellular signaling pathways involved. After pre-incubation of the Caco-2 cells with TNF-alpha and EPA for 1 hr, EPA prevented the inhibitory effect of the cytokine on alpha-methyl-D-glucose (alpha MG) uptake (15 min) and on SGLT1 expression at the brush border membrane, measured by Western blot. The ERK1/2 inhibitor PD98059 and the AMPK activator AICAR also prevented the inhibitory effect of TNF-alpha on both alpha MG uptake and SGLT1 expression. Interestingly, the AMPK inhibitor, Compound C, abolished the ability of EPA to prevent TNF-alpha-induced reduction of sugar uptake and transporter expression. The GPR120 antagonist, AH7614, also blocked the preventive effect of EPA on TNF-alpha-induced decrease of alpha MG uptake and AMPK phosphorylation. In summary, TNF-alpha inhibits alpha MG uptake by decreasing SGLT1 expression in the brush border membrane through the activation of ERK1/2 pathway. EPA prevents the inhibitory effect of TNF-alpha through the involvement of GPR120 and AMPK activation.