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Review
. 2010 Oct;24(10):1891-903.
doi: 10.1210/me.2010-0015. Epub 2010 Apr 14.

Minireview: Nuclear hormone receptor 4A signaling: implications for metabolic disease

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Review

Minireview: Nuclear hormone receptor 4A signaling: implications for metabolic disease

Michael A Pearen et al. Mol Endocrinol. 2010 Oct.

Abstract

Numerous members of the nuclear hormone receptor (NR) superfamily have been demonstrated to regulate metabolic function in a cell- and tissue-specific manner. This review brings together recent studies that have associated members of the NR superfamily, the orphan NR4A subgroup, with the regulation of metabolic function and disease. The orphan NR4A subgroup includes Nur77 (NR4A1), Nurr1 (NR4A2), and Nor-1 (NR4A3). Expression of these receptors is induced in multiple tissues by a diverse range of stimuli, including stimuli associated with metabolic function, such as: β-adrenoceptor agonists, cold, fatty acids, glucose, insulin, cholesterol, and thiazolidinediones. In vitro and in vivo gain- and loss-of-function studies in major metabolic tissues (including skeletal muscle, adipose, and liver cells and tissues) have associated the NR4A subgroup with specific aspects of lipid, carbohydrate, and energy homeostasis. Most excitingly, although these orphan receptors do not have known endogenous ligands, several small molecule agonists have recently been identified. The preliminary studies reviewed in this manuscript suggest that therapeutic exploitation of the NR4A subgroup may show utility against dyslipidemia, obesity, diabetes, and cardiovascular disease.

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Figures

Fig. 1.
Fig. 1.
Skeletal formula of the NR4A agonists. The published compounds that modulate the activity of the NR4 subgroup are: (A) 6-mercaptopurine, (B) prostaglandin A2, (C) cytosporone B, (D) 1,1-di(3′-indolyl)-1-(p-substituted phenyl)methane derivatives, (E) isoxazolopyridinone derivatives, and (F) benzimidazole derivatives.
Fig. 2.
Fig. 2.
Summary of the studies describing tissue specific NR4A activity in the context of metabolism.

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References

    1. Lau LF, Nathans D1985. Identification of a set of genes expressed during the G0/G1 transition of cultured mouse cells. EMBO J 4:3145–3151 - PMC - PubMed
    1. Hazel TG, Nathans D, Lau LF1988. A gene inducible by serum growth factors encodes a member of the steroid and thyroid hormone receptor superfamily. Proc Natl Acad Sci USA 85:8444–8448 - PMC - PubMed
    1. Milbrandt J1988. Nerve growth factor induces a gene homologous to the glucocorticoid receptor gene. Neuron 1:183–188 - PubMed
    1. Law SW, Conneely OM, DeMayo FJ, O'Malley BW1992. Identification of a new brain-specific transcription factor, NURR1. Mol Endocrinol 6:2129–2135 - PubMed
    1. Ohkura N, Hijikuro M, Yamamoto A, Miki K1994. Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells. Biochem Biophys Res Commun 205:1959–1965 - PubMed

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