Impairment of miR-142-3p-mediated downregulation of glucocorticoid receptor expression in high fat diet-induced obese rats

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 72-87-HPA Axis
Basic
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-81
Takahiro Nemoto*1 and Tamotsu Shibasaki2
1Nippon Med Schl, Tokyo, Japan, 2Nippon Med Sch, Tokyo, Japan
Obesity is found to increase the risk of depression. A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is shown in depression. The hormones composing the HPA axis play important roles in stress response. The HPA axis is controlled by the feedback of glucocortioids on the hypothalamus, hippocampus and pituitary. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate the expression of target genes at the post-transcriptional level. It has been demonstrated that there are at least three miRNAs (miR-101a, miR-124, miR-142-3p) with sequences capable of binding to glucocorticoid receptor (GR) 3’-untranslated region. However, their involvement in stress-induced downregulation of GR expression and dysregulation of the HPA axis function in high fat diet-induced obesity (DIO) are unclear. The aim of this study is to identify which miRNAs are involved in restraint-induced downregulation of GR expression in the hypothalamus and the hippocampus of normal rats, and to compare the basal levels and restraint-induced change of miRNA expressions in those tissues in control and DIO rats. In control rats, restraint significantly increased plasma corticosterone concentrations at 30 min which were lowered at 90 and 120 min while it significantly decreased GR mRNA and protein expressions, and significantly increased the expression of miR-142-3p in the hypothalamus and the hippocampus without changing the expression of miR-101a and miR-124. In DIO rats, the basal levels and the elevated levels after restraint of plasma corticosterone were significantly higher than those in control rats at 30, 90 and 120 min. Although there were no differences in the basal expression of GR mRNA and protein or miR-142-3p in the hypothalamus and the hippocampus between DIO and control rats, restraint induced no significant changes in GR mRNA and protein or the expression of miR-142-3p in the hypothalamus and the hippocampus in DIO rats. The results suggest that miR-142-3p is probably involved in restraint-induced downregulation of GR expression and that high fat diet-induced obesity causes prolongation of restraint-induced elevation of plasma corticosterone concentrations probably through an impairment of miR-142-3p expression in the hypothalamus and the hippocampus.

Nothing to Disclose: TN, TS

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