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.

中文翻译：

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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。

在肥胖症和 2 型糖尿病中，许多基因存在差异表达，并且 microRNA 参与靶 mRNA 的转录调控，但与食欲控制密切相关的 miRNA 尚不清楚。在这里，我们通过 RNA 测序鉴定了喂食高脂肪高蔗糖 (HFHS) 食物的 C57BL/6 小鼠的大脑和脂肪组织中 miR-342-3p 及其宿主基因 Evl 的上调。喂食 HFHS 食物的 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。在 Mir342 (-/-) 小鼠中，活化的 NPY+pSTAT3+ 神经元的百分比降低，而 POMC+pSTAT3+ 神经元增加，它们表明食物摄入减少和代谢表型改善。Snap25 被确定为 miR-342-3p 的主要靶基因，Snap25 的表达降低可能与下丘脑神经元功能障碍和食物摄入过多有关。抑制 miR-342-3p 可能是基于 miRNA 的治疗的潜在候选者。