The nuclear receptor, Nor-1, induces the physiological responses associated with excercise

Goode, Joel M., Pearen, Michael A., Tuong, Zewen K., Wang, Shu-Ching M., Oh, Tae Gyu, Shao, Emily X. and Muscat, George E. (2016) The nuclear receptor, Nor-1, induces the physiological responses associated with excercise. Molecular Endocrinology, 30 6: 660-676. doi:10.1210/me.2015-1300

Author Goode, Joel M.
Pearen, Michael A.
Tuong, Zewen K.
Wang, Shu-Ching M.
Oh, Tae Gyu
Shao, Emily X.
Muscat, George E.
Title The nuclear receptor, Nor-1, induces the physiological responses associated with excercise
Journal name Molecular Endocrinology   Check publisher's open access policy
ISSN 0888-8809
Publication date 2016-05-04
Year available 2016
Sub-type Article (original research)
DOI 10.1210/me.2015-1300
Open Access Status Not Open Access
Volume 30
Issue 6
Start page 660
End page 676
Total pages 16
Place of publication Chevy Chase, MD United States
Publisher The Endocrine Society
Language eng
Subject 1312 Molecular Biology
1310 Endocrinology
Abstract Skeletal muscle remodels metabolic capacity, contractile and exercise phenotype in response to physiological demands. This adaptive remodeling response to physical activity can ameliorate/prevent diseases associated with poor diet and lifestyle. Our previous work demonstrated that skeletal muscle-specific transgenic expression of the neuron-derived orphan nuclear receptor, Nor-1 drives muscle reprogramming, improves exercise endurance, and oxidative metabolism. The current manuscript investigates the association between exercise, Nor-1 expression and the role of Nor-1 in adaptive remodeling. We demonstrate that Nor-1 expression is induced by exercise and is dependent on calcium/calcineurin signaling (in vitro and in vivo). Analysis of fatigue-resistant transgenic mice that express Nor-1 in skeletal muscle revealed increased hypertrophy and vascularization of muscle tissue. Moreover, we demonstrate that transgenic Nor-1 expression is associated with increased intracellular recycling, ie, autophagy, involving 1) increased expression of light chain 3A or LC3A-II, autophagy protein 5, and autophagy protein 12 in quadriceps femoris muscle extracts from Tg-Nor-1 (relative to Wild-type (WT) littermates); 2) decreased p62 expression indicative of increased autophagolysosome assembly; and 3) decreased mammalian target of rapamycin complex 1 activity. Transfection of LC3A-GFP-RFP chimeric plasmid demonstrated that autophagolysosome formation was significantly increased by Nor-1 expression. Furthermore, we demonstrated a single bout of exercise induced LC3A-II expression in skeletal muscle from C57BL/6 WT mice. This study, when combined with our previous studies, demonstrates that Nor-1 expression drives multiple physiological changes/pathways that are critical to the beneficial responses of muscle to exercise and provides insights into potential pharmacological manipulation of muscle reprogramming for the treatment of lifestyle induced chronic diseases.
Keyword Endocrinology & Metabolism
Endocrinology & Metabolism
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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Created: Mon, 13 Jun 2016, 20:29:19 EST by Susan Allen on behalf of Institute for Molecular Bioscience