The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle

Pearen, Michael A., Ryall, James G., Maxwell, Megan A., Ohkura, Naganari, Lynch, Gordon S. and Muscat, George E. O. (2006) The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle. Endocrinology, 147 11: 5217-5227. doi:10.1210/en.2006-0447

Author Pearen, Michael A.
Ryall, James G.
Maxwell, Megan A.
Ohkura, Naganari
Lynch, Gordon S.
Muscat, George E. O.
Title The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1210/en.2006-0447
Open Access Status Not Open Access
Volume 147
Issue 11
Start page 5217
End page 5227
Total pages 11
Editor Jeffrey E. Pessin
Place of publication Chevy Chase
Publisher Endocrine Society
Language eng
Subject C1
321004 Endocrinology
730105 Endocrine organs and diseases (incl. diabetes)
Abstract beta-Adrenergic receptor (beta-AR) agonists induce Nur77 mRNA expression in the C2C12 skeletal muscle cell culture model and elicit skeletal muscle hypertrophy. We previously demonstrated that Nur77 (NR4A1) is involved in lipolysis and gene expression associated with the regulation of lipid homeostasis. Subsequently it was demonstrated by another group that beta-AR agonists and cold exposure-induced Nur77 expression in brown adipocytes and brown adipose tissue, respectively. Moreover, NOR-1 (NR4A3) was hyperinduced by cold exposure in the nur77(-/-) animal model. These studies underscored the importance of understanding the role of NOR-1 in skeletal muscle. In this context we observed 30-480 min of beta-AR agonist treatment significantly and transiently increased expression of the orphan nuclear receptor NOR-1 in both mouse skeletal muscle tissue (plantaris) and C2C12 skeletal muscle cells. Specific beta(2)-and beta(3)-AR agonists had similar effects as the pan-agonist and were blocked by the beta-AR antagonist propranolol. Moreover, in agreement with these observations, isoprenaline also significantly increased the activity of the NOR-1 promoter. Stable exogenous expression of a NOR-1 small interfering RNA (but not the negative control small interfering RNA) in skeletal muscle cells significantly repressed endogenous NOR-1 mRNA expression and led to changes in the expression of genes involved in the control of lipid use and muscle mass underscored by a dramatic increase in myostatin mRNA expression. Concordantly the myostatin promoter was repressed by NOR-1 expression. In conclusion, NOR-1 is highly responsive to beta-adrenergic signaling and regulates the expression of genes controlling fatty acid use and muscle mass.
Keyword muscle tissue
fatty tissue
Uncoupling Protein-3
Beta-3-adrenergic Agonist
Q-Index Code C1

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Created: Wed, 15 Aug 2007, 19:22:22 EST