Loss of NOR-1 represses muscle metabolism through mTORC1-mediated signaling and mitochondrial gene expression in C2C12 myotubes.

Autor: Paez HG; Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Integrated Biomedical Sciences Graduate Program, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Laboratory of Muscle Biology and Sarcopenia, Department of Physical Therapy, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Division of Regenerative and Rehabilitation Sciences, Center for Muscle, Metabolism and Neuropathology, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, USA., Ferrandi PJ; Integrated Biomedical Sciences Graduate Program, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Division of Regenerative and Rehabilitation Sciences, Center for Muscle, Metabolism and Neuropathology, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Laboratory of Muscle and Nerve, Department of Diagnostic and Health Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, USA., Pitzer CR; Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Integrated Biomedical Sciences Graduate Program, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Laboratory of Muscle Biology and Sarcopenia, Department of Physical Therapy, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Division of Regenerative and Rehabilitation Sciences, Center for Muscle, Metabolism and Neuropathology, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, USA., Mohamed JS; Integrated Biomedical Sciences Graduate Program, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Division of Regenerative and Rehabilitation Sciences, Center for Muscle, Metabolism and Neuropathology, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Laboratory of Muscle and Nerve, Department of Diagnostic and Health Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, USA., Alway SE; Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Integrated Biomedical Sciences Graduate Program, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Laboratory of Muscle Biology and Sarcopenia, Department of Physical Therapy, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, USA.; Division of Regenerative and Rehabilitation Sciences, Center for Muscle, Metabolism and Neuropathology, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2023 Aug; Vol. 37 (8), pp. e23050.
DOI: 10.1096/fj.202202029R
Abstrakt: 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.
(© 2023 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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