Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control.

Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control.
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饮食诱导的肥胖小鼠和下丘脑食欲控制中miR342的上调。

DOI:
10.3389/fendo.2021.727915
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发表时间:
2021
影响因子:
5.2
通讯作者:
Wada J
Wada J
中科院分区:
医学2区
文献类型:
--
作者:
Zhang D;Yamaguchi S;Zhang X;Yang B;Kurooka N;Sugawara R;Albuayjan HHH;Nakatsuka A;Eguchi J;Hiyama TY;Kamiya A;Wada J

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在肥胖和2型糖尿病中,许多基因有差异表达,microRNAs参与靶mRNAs的转录调控,但关键参与食欲控制的miRNAs尚不清楚。在这里,我们通过RNA测序发现,在高脂-高蔗糖(HFHS)饲料喂养的C57BL/6小鼠脑和脂肪组织中miR-342-3p及其宿主基因EVL表达上调。用HFHS食物喂养的Mir342(-/-)小鼠免受肥胖和糖尿病的影响。下丘脑弓状核神经元共同表达Mir342和EVL。Mir342(-/-)小鼠激活的NPY+pSTAT3+神经元百分率降低,POMC+pSTAT3+神经元百分率增加,摄食量减少,代谢表型改善。Snap25被确定为miR-342-3p的主要靶基因,Snap25表达降低可能与下丘脑神经元功能障碍和食物摄入量过多有关。MiR-342-3p的抑制可能是miRNA治疗的一个潜在候选基因。
In obesity and type 2 diabetes, numerous genes are differentially expressed, and microRNAs are involved in transcriptional regulation of target mRNAs, but miRNAs critically involved in the appetite control are not known. Here, we identified upregulation of miR-342-3p and its host gene Evl in brain and adipose tissues in C57BL/6 mice fed with high fat-high sucrose (HFHS) chow by RNA sequencing. Mir342 (-/-) mice fed with HFHS chow were protected from obesity and diabetes. The hypothalamic arcuate nucleus neurons co-express Mir342 and EVL. The percentage of activated NPY+pSTAT3+ neurons were reduced, while POMC+pSTAT3+ neurons increased in Mir342 (-/-) mice, and they demonstrated the reduction of food intake and amelioration of metabolic phenotypes. Snap25 was identified as a major target gene of miR-342-3p and the reduced expression of Snap25 may link to functional impairment hypothalamic neurons and excess of food intake. The inhibition of miR-342-3p may be a potential candidate for miRNA-based therapy.
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