Article ; Online: Loss of NOR-1 represses muscle metabolism through mTORC1-mediated signaling and mitochondrial gene expression in C2C12 myotubes.
2023 Volume 37, Issue 8, Page(s) e23050
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 ... ...
| 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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| MeSH term(s) | Humans ; Diabetes Mellitus, Type 2 ; Gene Expression ; Genes, Mitochondrial ; Insulin Resistance ; Mechanistic Target of Rapamycin Complex 1/genetics ; Muscle Fibers, Skeletal ; Muscle, Skeletal ; Obesity/genetics |
| Chemical Substances | 1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole (145757-47-7) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; NR4A3 protein, human |
| Language | English |
| Publishing date | 2023-06-30 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. |
| ZDB-ID | 639186-2 |
| ISSN | 1530-6860 ; 0892-6638 |
| ISSN (online) | 1530-6860 |
| ISSN | 0892-6638 |
| DOI | 10.1096/fj.202202029R |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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