The nuclear receptor, Nor-1, markedly increases type II oxidative muscle fibers and resistance to fatigue

Pearen, Michael A., Eriksson, Natalie A., Fitzsimmons, Rebecca L., Goode, Joel M., Martel, Nick, Andrikopoulos, Sofianos and Muscat, George E. O. (2012) The nuclear receptor, Nor-1, markedly increases type II oxidative muscle fibers and resistance to fatigue. Molecular Endocrinology, 26 3: 372-384. doi:10.1210/me.2011-1274

Author Pearen, Michael A.
Eriksson, Natalie A.
Fitzsimmons, Rebecca L.
Goode, Joel M.
Martel, Nick
Andrikopoulos, Sofianos
Muscat, George E. O.
Title The nuclear receptor, Nor-1, markedly increases type II oxidative muscle fibers and resistance to fatigue
Journal name Molecular Endocrinology   Check publisher's open access policy
ISSN 0888-8809
Publication date 2012-03
Sub-type Article (original research)
DOI 10.1210/me.2011-1274
Volume 26
Issue 3
Start page 372
End page 384
Total pages 13
Place of publication Chevy Chase, MD, United States
Publisher The Endocrine Society
Collection year 2013
Language eng
Abstract Nuclear hormone receptors (NR) have been implicated as regulators of lipid and carbohydrate metabolism. The orphan NR4A subgroup has emerged as regulators of metabolic function. Targeted silencing of neuron-derived orphan receptor 1 (Nor-1)/NR4A3 in skeletal muscle cells suggested that this NR was necessary for oxidative metabolism in vitro. To investigate the in vivo role of Nor-1, we have developed a mouse model with preferential expression of activated Nor-1 in skeletal muscle. In skeletal muscle, this resulted in a marked increase in: 1) myoglobin expression, 2) mitochondrial DNA and density, 3) oxidative enzyme staining, and 4) genes/proteins encoding subunits of electron transport chain complexes. This was associated with significantly increased type IIA and IIX myosin heavy chain mRNA and proteins and decreased type IIB myosin heavy chain mRNA and protein. The contractile protein/fiber type remodeling driving the acquisition of the oxidative type II phenotype was associated with 1) the significantly increased expression of myocyte-specific enhancer factor 2C, and phospho-histone deacetylase 5, and 2) predominantly cytoplasmic HDAC5 staining in the Tg-Nor-1 mice. Moreover, the Nor-1 transgenic line displayed significant improvements in glucose tolerance, oxygen consumption, and running endurance (in the absence of increased insulin sensitivity), consistent with increased oxidative capacity of skeletal muscle. We conclude that skeletal muscle fiber type is not only regulated by exercise-sensitive calcineurin-induced signaling cascade but also by NR signaling pathways that operate at the nexus that coordinates muscle performance and metabolic capacity in this major mass tissue.
Keyword Human Skeletal-Muscle
Metabolic Gene-Expression
Myosin Heavy-Chains
Histone Deacetylases
Transgenic Mice
Actin Gene
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print 26 January 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
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