Glucose and Palmitate Differentially Regulate PFKFB3/iPFK2 and Inflammatory Responses in Mouse Intestinal Epithelial Cells.
Glucose and Palmitate Differentially Regulate PFKFB3/iPFK2 and Inflammatory Responses in Mouse Intestinal Epithelial Cells.
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DOI：
10.1038/srep28963
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发表时间：
2016-07-08
影响因子：
4.6
通讯作者：
Wu C
中科院分区：
文献类型：
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作者：
Botchlett R;Li H;Guo X;Qi T;Zhao J;Zheng J;Woo SL;Pei Y;Liu M;Hu X;Chen G;Guo T;Yang S;Li Q;Xiao X;Huo Y;Wu C
基因PFKFB 3编码诱导型6-磷酸果糖-2-激酶，这是一种糖酵解调节酶，可防止饮食诱导的肠道炎症。然而，目前还不清楚营养超载如何调节肠上皮细胞（IEC）中PFKFB 3的表达和炎症反应。在本研究中，原代IEC分离自喂食低脂饮食（LFD）或高脂饮食（HFD）12周的C57 BL/6 J小鼠的小肠。另外，将培养于低糖（LG，5.5 mmol/L）或高糖（HG，27.5 mmol/L）培养基中的肠上皮细胞系CMT-93细胞分别用棕榈酸（50 μmol/L）或牛血清白蛋白（BSA）处理24 h。分析这些细胞的PFKFB 3和炎症标志物。与LFD相比，HFD喂养降低IEC PFKFB 3表达，增加IEC促炎反应。在CMT-93细胞，HG显着增加PFKFB 3的表达和促炎反应相比，LG。有趣的是，棕榈酸降低PFKFB 3的表达和增加促炎反应相比，BSA，无论葡萄糖浓度。此外，HG显着增加PFKFB 3启动子转录活性与LG相比。PFKFB 3过表达后，CMT-93细胞的促炎反应降低。总之，这些结果表明，在IEC中，葡萄糖刺激PFKFB 3表达，棕榈酸酯有助于增加促炎反应。因此，PFKFB 3调节IEC炎症状态以响应大量营养素。
The gene PFKFB3 encodes for inducible 6-phosphofructo-2-kinase, a glycolysis-regulatory enzyme that protects against diet-induced intestine inflammation. However, it is unclear how nutrient overload regulates PFKFB3 expression and inflammatory responses in intestinal epithelial cells (IECs). In the present study, primary IECs were isolated from small intestine of C57BL/6J mice fed a low-fat diet (LFD) or high-fat diet (HFD) for 12 weeks. Additionally, CMT-93 cells, a cell line for IECs, were cultured in low glucose (LG, 5.5 mmol/L) or high glucose (HG, 27.5 mmol/L) medium and treated with palmitate (50 μmol/L) or bovine serum albumin (BSA) for 24 hr. These cells were analyzed for PFKFB3 and inflammatory markers. Compared with LFD, HFD feeding decreased IEC PFKFB3 expression and increased IEC proinflammatory responses. In CMT-93 cells, HG significantly increased PFKFB3 expression and proinflammatory responses compared with LG. Interestingly, palmitate decreased PFKFB3 expression and increased proinflammatory responses compared with BSA, regardless of glucose concentrations. Furthermore, HG significantly increased PFKFB3 promoter transcription activity compared with LG. Upon PFKFB3 overexpression, proinflammatory responses in CMT-93 cells were decreased. Taken together, these results indicate that in IECs glucose stimulates PFKFB3 expression and palmitate contributes to increased proinflammatory responses. Therefore, PFKFB3 regulates IEC inflammatory status in response to macronutrients.