Dietary obesity and glycemic excursions cause a parallel increase in STEAP4 and pro-inflammatory gene expression in murine PBMCs
Dietary obesity and glycemic excursions cause a parallel increase in STEAP4 and pro-inflammatory gene expression in murine PBMCs
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DOI：
10.1007/s13340-021-00542-1
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发表时间：
2021-09
影响因子：
2.2
通讯作者：
Sigfrid Casmir Shayo;Kazuma Ogiso;Shigeru Kawade;H. Hashiguchi;T. Deguchi;Y. Nishio
中科院分区：
文献类型：
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作者：
Sigfrid Casmir Shayo;Kazuma Ogiso;Shigeru Kawade;H. Hashiguchi;T. Deguchi;Y. Nishio
背景促动脉粥样硬化因子和抗动脉粥样硬化因子之间的平衡在动脉粥样硬化病变的发展过程中起着至关重要的作用。虽然已知骨髓细胞中前列腺6跨膜上皮抗原4（STEAP 4）的表达具有动脉粥样硬化保护作用，但没有一项研究报道在饮食诱导的肥胖的早期阶段或血糖波动事件中循环单核细胞中STEAP 4表达的状态。结果饮食诱导的肥胖和血糖波动独立地引起外周血单核细胞STEAP 4 mRNA表达的显著增加。这也伴随着大量促炎细胞因子，趋化因子，然而，西方饮食和高血糖峰值的联合作用是微妙的和非加性的。在体外环境中，无论是葡萄糖峰值，持续的高血糖，还是棕榈酸和胰岛素的组合，都导致STEAP 4和促炎基因表达的平行增加。然而，用衣康酸4-辛酯显著消除或用p38 MAPK和NF-κ B抑制剂减弱。结论STEAP 4在单核细胞中的表达是由炎症或氧化应激引起的，内脏肥胖或血糖波动引起的STEAP 4在循环单核细胞中的表达增加是一个重要的因素。代偿反应
BackgroundThe balance between pro-atherogenic and anti-atherogenic factors is very crucial in the development of atherosclerotic lesions. Although the expression of the six-transmembrane epithelial antigen of the prostate 4 (STEAP4) in myeloid cells is known to be atheroprotective, there is not a single study reporting on the status of STEAP4 expression in circulating monocytes in the early stages of diet-induced obesity or in events of glycemic excursions.MethodsWe induced glycemic spikes twice daily for a 1-week duration to rats fed on regular chow and western diet, and analyzed gene expression changes in the peripheral blood mononuclear cells (PBMCs). We also conducted experiments on RAW 264.7 cells to gain insight into some of our in vivo findings.ResultsDiet-induced obesity and glycemic excursions independently caused a significant increase in STEAP4 mRNA expression in PBMCs. This was also accompanied by an induction of a substantial number of pro-inflammatory cytokines, chemokines, and chemokine receptors. However, the combined effect of western diet and hyperglycemic spikes was subtle and non-additive. In the in vitro setting, either glucose spikes, persistent hyperglycemia, or a combination of palmitic acid and insulin resulted in a parallel increase in expression of STEAP4 and pro-inflammatory genes. This was, however, significantly abrogated with 4-octyl itaconate or attenuated by inhibitors of p38MAPK and NF-kB.ConclusionsSTEAP4 expression in mononuclear cells is induced by increasing inflammation or oxidative stress. The observed increase in STEAP4 expression in circulating monocytes due to visceral obesity or glycemic excursions is a compensatory response.