Nr4a1 siRNA expression attenuates alpha-MSH regulated gene expression in 3T3-L1 adipocytes

Wang, Scm, Myers, SA, Eriksson, NA, Fitzsimmons, RL and Muscat, GEO (2011) Nr4a1 siRNA expression attenuates alpha-MSH regulated gene expression in 3T3-L1 adipocytes. Molecular Endocrinology, 25 2: 291-306. doi:10.1210/me.2010-0231

Author Wang, Scm
Myers, SA
Eriksson, NA
Fitzsimmons, RL
Muscat, GEO
Title Nr4a1 siRNA expression attenuates alpha-MSH regulated gene expression in 3T3-L1 adipocytes
Journal name Molecular Endocrinology   Check publisher's open access policy
ISSN 0888-8809
Publication date 2011-02-01
Year available 2011
Sub-type Article (original research)
DOI 10.1210/me.2010-0231
Volume 25
Issue 2
Start page 291
End page 306
Total pages 16
Place of publication Chevy Chase MD, United States
Publisher The Endocrine Society
Language eng
Formatted abstract
Several recent investigations have underscored the growing role of melanocortin signaling in the peripheral regulation of lipid, glucose, and energy homeostasis. In addition, the melanocortins play a critical role in the central control of satiety. These observations, and the latest reports highlighting the emerging role of the nuclear hormone receptor (NR) 4A subgroup in metabolism, have prompted us to investigate the cross talk between [Nle4, d-Phe7] (NDP)-α-MSH and Nr4a signaling in adipose. We have shown that NDP-MSH strikingly and preferentially induces the expression of the NR4A subgroup (but not any other members of the NR superfamily) in differentiated 3T3-L1 adipocytes. Utilization of quantitative PCR on custom-designed metabolic TaqMan low-density arrays identified the concomitant and marked induction of the mRNAs encoding Il-6, Cox2, Pdk4, and Pck-1 after NDP-MSH treatment. Similar experiments demonstrated that the mRNA expression profile induced by cAMP and NDP-MSH treatment displayed unique but also overlapping properties and suggested that melanocortin-mediated induction of gene expression involves cAMP-dependent and -independent signaling. Nr4a1/Nur77 small interfering RNA (siRNA) expression suppressed NDP-MSH-mediated induction of Nr4a1/Nur77 and Nr4a3/Nor-1 (but not Nr4a2/Nurr1). Moreover, expression of the siRNA-attenuated NDP-MSH mediated induction of the mRNAs encoding Il-6, Cox2/Ptgs2, and Pck-1 expression. In addition, Nur77 siRNA expression attenuated NDP-MSH-mediated glucose uptake. In vivo, ip administration of NDP-MSH to C57 BL/6J (male) mice significantly induced the expression of the mRNA encoding Nur77 and increased IL-6, Cox2, Pck1, and Pdk4 mRNA expression in (inguinal) adipose tissue. We conclude that Nur77 expression is necessary for MSH-mediated induction of gene expression in differentiated adipocytes. Furthermore, this study demonstrates cross talk between MSH and Nr4a signaling in adipocytes.
Keyword Orphan Nuclear Receptor
Central melanocortin system
Insulin action
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print January 14, 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
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Created: Sun, 27 Feb 2011, 10:04:42 EST