Restraint-induced glucocorticoid receptor downregulation is dysregulated in high fat diet-fed rats likely from impairment of miR-142-3p expression in the hypothalamus and hippocampus.
Restraint-induced glucocorticoid receptor downregulation is dysregulated in high fat diet-fed rats likely from impairment of miR-142-3p expression in the hypothalamus and hippocampus.
复制标题
在高脂肪饮食喂养的大鼠中，约束诱导的糖皮质激素受体下调失调，可能是由于下丘脑和海马中 miR-142-3p 表达受损。
DOI：
10.11648/j.ajls.s.2015030302.15
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Shibasaki T.
中科院分区：
文献类型：
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作者：
Nemoto T;Kakinuma Y;Shibasaki T.
高脂饮食（HFD）可导致下丘脑-垂体-肾上腺（HPA）轴功能失调。HPA轴受下丘脑、海马和垂体上的糖皮质激素反馈控制。至少有三种miRNA（miR-101 a、miR-124、miR-142- 3 p）被报道抑制糖皮质激素受体（GR）的翻译。由于它们与应激诱导的GR表达下调及其在HFD喂养中表达失调的关系尚不清楚，我们研究了哪些miRNA参与了限制诱导的下丘脑和海马GR表达下调，并比较了HFD喂养大鼠这些组织中基础和限制修饰的miRNA表达。将暴露于HFD的大鼠分为两组，HFD诱导的肥胖（HFD-ob）和肥胖抵抗（HFD-obR）大鼠。基础血浆皮质酮浓度在HFD-ob中高于标准饲料喂养（SC）大鼠和HFD-obR。HFD-obR组的血浆皮质酮水平高于其他组。束缚降低了下丘脑和海马GR的表达，增加了miR-142- 3 p的表达，但对其他部位的表达无影响。地塞米松增加了两个区域中的miR-142- 3 p表达，并且在肾上腺切除术中抑制诱导的miR-142- 3 p表达被阻断。HFD喂养大鼠的两个区域中GR或miR-142- 3 p表达的基础表达与SC的基础表达没有差异，并且束缚在HFD-ob和HFD-obR的两个区域中均未诱导GR或miR-142- 3 p表达的变化。这些结果表明，糖皮质激素诱导的miR-142- 3 p增加的损害可能涉及HFD喂养大鼠下丘脑和海马中应激诱导的GR表达下调的失调。
High fat diet (HFD) induces dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function. The HPA axis is controlled by the feedback of glucocortioids on the hypothalamus, hippocampus and pituitary. At least three miRNAs (miR-101a, miR-124, miR-142-3p) have been reported to suppress glucocorticoid receptor (GR) translation. Because their relation to stress-induced downregulation of GR expression and dysregulation of its expression in HFD feeding are unclear, we studied to identify which miRNAs are involved in restraint-induced downregulation of GR expression in the hypothalamus and hippocampus, and to compare the basal and restraint-modified miRNA expressions in these tissues in HFD-fed rats. Rats exposed to HFD were divided into two groups, HFD-induced obese (HFD-ob) and obesity resistant (HFD-obR) rats. Basal plasma corticosterone concentrations were higher in HFD-ob than in standard chow-fed (SC) rats and in HFD-obR. Restraint-induced elevation of plasma corticosterone was higher in HFD-obR than in the other groups. Restraint decreased GR expressions and increased miR-142-3p expression in the hypothalamus and hippocampus without affecting others expressions. miR-142-3p expressions in both areas were increased by dexamethasone and restraint-induced miR-142-3p expression was blocked in adrenalectomy. The basal expression of GR or miR-142-3p expression in both areas of HFD-fed rats did not differ from those of SC, and restraint induced no changes in GR or miR-142-3p expression in both areas in HFD-ob and HFD-obR. These results suggest that impairment of glucocorticoid-induced increase in miR-142-3p may be involved in dysregulation of stress-induced downregulation of GR expression in the hypothalamus and hippocampus of HFD-fed rats.