肌发生
基因敲除
骨骼肌
mTORC1型
胰岛素受体
胰岛素抵抗
生物
信号转导
C2C12型
心肌细胞
细胞生物学
内分泌学
PI3K/AKT/mTOR通路
基因
胰岛素
生物化学
作者
Hector G. Paez,Peter J. Ferrandi,Christopher R. Pitzer,Junaith S. Mohamed,Stephen E. Alway
标识
DOI:10.1096/fj.202202029r
摘要
Abstract Gene expression of the NR4A nuclear orphan receptor NOR‐1 is reduced in obesity and in human skeletal muscle during disuse. It has been well established that NOR‐1 is highly responsive to both aerobic and resistance exercise and NOR‐1 overexpression is coincident with a plethora of metabolic benefits. However, it is unclear whether loss of NOR‐1 contributes to inappropriate metabolic signaling in skeletal muscle that could lead to insulin resistance. The purpose of this study was to elucidate the impact of NOR‐1 deficiency on C2C12 metabolic signaling. Changes in gene expression after siRNA‐mediated NOR‐1 knockdown in C2C12 myotubes were determined by qPCR and bioinformatic analysis of RNA‐Seq data. Our RNA‐Seq data identified several metabolic targets regulated by NOR‐1 and implicates NOR‐1 as a modulator of mTORC1 signaling via Akt‐independent mechanisms. Furthermore, pathway analysis revealed NOR‐1 knockdown perturbs the insulin resistance and insulin sensitivity pathways. Taken together, these data suggest skeletal muscle NOR‐1 deficiency may contribute to altered metabolic signaling that is consistent with metabolic disease. We postulate that strategies that improve NOR‐1 may be important to offset the negative impact that inactivity, obesity, and type 2 diabetes have on mitochondria and muscle metabolism.
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