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Unveiling the transcriptome alteration of POMC neuron in diet-induced obesity.
Experimental Cell Research ( IF 3.3 ) Pub Date : 2020-01-16 , DOI: 10.1016/j.yexcr.2020.111848
Peng Lyu 1 , Zhishun Huang 1 , Qingjun Feng 1 , Yongfu Su 1 , Mengying Zheng 1 , Yannv Hong 1 , Xiang Cai 1 , Zhonglei Lu 1
Affiliation  

Loss of neuron homeostasis in the arcuate nucleus (ARC) is responsible for diet-induced-obesity (DIO). We previously reported that loss of Rb1 gene compromised the homeostasis of anorexigenic POMC neurons in ARC and induced obesity in mice. To evaluate the development of DIO, we propose to analyze the transcriptomic alteration of POMC neurons in mice following high fat diet (HFD) feeding. We isolated these neurons from established DIO mice and performed transcriptomic profiling using RNA-seq. In total, 1066 genes (628 upregulated and 438 downregulated) were identified as differentially expressed genes (DEGs). Pathway enrichment analysis with these DEGs further revealed that "cell cycle," "apoptosis," "chemokine signaling," and "sphingolipid metabolism" pathways were correlated with DIO development. Moreover, we validated that the pRb protein, a key regulator of "cell cycle pathway," was inactivated by phosphorylation in POMC neurons by HFD feeding. Importantly, the reversal of deregulated cell cycle by stereotaxic delivering of the unphosphorylated pRbΔP in ARC significantly meliorated the DIO. Collectively, our study provides insights into the mechanisms related to the loss of homeostasis of POMC neurons in DIO, and suggests pRb phosphorylation as a potential intervention target to treat DIO.

中文翻译:

揭示饮食引起的肥胖症中POMC神经元的转录组改变。

弓形核(ARC)中神经元稳态的丧失是饮食引起的肥胖症(DIO)的原因。我们以前曾报道说Rb1基因的丢失损害了ARC中的厌食性POMC神经元的稳态,并在小鼠中诱发了肥胖。为了评估DIO的发展,我们建议分析高脂饮食(HFD)喂养后小鼠POMC神经元的转录组变化。我们从已建立的DIO小鼠中分离了这些神经元,并使用RNA-seq进行了转录组分析。总共鉴定出1066个基因(上调628个,下调438个)为差异表达基因(DEG)。用这些DEG进行的途径富集分析进一步表明,“细胞周期”,“凋亡”,“趋化因子信号传导”和“鞘脂代谢”途径与DIO的发展有关。此外,我们验证了通过HFD喂食,POMC神经元中的磷酸化使pRb蛋白(“细胞周期途径”的关键调节剂)失活。重要的是,通过ARC中未磷酸化的pRbΔP的立体定向递送,逆转了失调的细胞周期,大大改善了DIO。总的来说,我们的研究提供了与DIO中POMC神经元稳态丧失相关的机制的见解,并建议pRb磷酸化作为治疗DIO的潜在干预目标。
更新日期:2020-01-16
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