Unveiling the transcriptome alteration of POMC neuron in diet-induced obesity

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 t...

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Veröffentlicht in:Experimental cell research 2020-04, Vol.389 (1), p.111848-111848, Article 111848
Hauptverfasser: Lyu, Peng, Huang, Zhishun, Feng, Qingjun, Su, Yongfu, Zheng, Mengying, Hong, Yannv, Cai, Xiang, Lu, Zhonglei
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container_issue 1
container_start_page 111848
container_title Experimental cell research
container_volume 389
creator Lyu, Peng
Huang, Zhishun
Feng, Qingjun
Su, Yongfu
Zheng, Mengying
Hong, Yannv
Cai, Xiang
Lu, Zhonglei
description 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.
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subjects Diet-induced obesity (DIO)
High-fat-diet (HFD)
Neuron homeostasis
POMC neuron
pRb phosphorylation
title Unveiling the transcriptome alteration of POMC neuron in diet-induced obesity
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