Orphan nuclear receptors: therapeutic opportunities in skeletal muscle

Smith, Aaron G. and Muscat, George E. O. (2006) Orphan nuclear receptors: therapeutic opportunities in skeletal muscle. American Journal of Physiology-cell Physiology, 291 2: C203-C217. doi:10.1152/ajpcell.00476.2005

Author Smith, Aaron G.
Muscat, George E. O.
Title Orphan nuclear receptors: therapeutic opportunities in skeletal muscle
Journal name American Journal of Physiology-cell Physiology   Check publisher's open access policy
ISSN 0363-6143
Publication date 2006
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1152/ajpcell.00476.2005
Volume 291
Issue 2
Start page C203
End page C217
Total pages 15
Editor Dennis Brown
Place of publication Bethesda
Publisher American Physiological Society
Collection year 2006
Language eng
Subject C1
321004 Endocrinology
730105 Endocrine organs and diseases (incl. diabetes)
Abstract Orphan nuclear receptors: therapeutic opportunities in skeletal muscle. Am J Physiol Cell Physiol 291: C203-C217, 2006; doi: 10.1152/ajpcell. 00476.2005.-Nuclear hormone receptors (NRs) are ligand-dependent transcription factors that bind DNA and translate physiological signals into gene regulation. The therapeutic utility of NRs is underscored by the diversity of drugs created to manage dysfunctional hormone signaling in the context of reproductive biology, inflammation, dermatology, cancer, and metabolic disease. For example, drugs that target nuclear receptors generate over $10 billion in annual sales. Almost two decades ago, gene products were identified that belonged to the NR superfamily on the basis of DNA and protein sequence identity. However, the endogenous and synthetic small molecules that modulate their action were not known, and they were denoted orphan NRs. Many of the remaining orphan NRs are highly enriched in energy-demanding major mass tissues, including skeletal muscle, brown and white adipose, brain, liver, and kidney. This review focuses on recently adopted and orphan NR function in skeletal muscle, a tissue that accounts for similar to 35% of the total body mass and energy expenditure, and is a major site of fatty acid and glucose utilization. Moreover, this lean tissue is involved in cholesterol efflux and secretes that control energy expenditure and adiposity. Consequently, muscle has a significant role in insulin sensitivity, the blood lipid profile, and energy balance. Accordingly, skeletal muscle plays a considerable role in the progression of dyslipidemia, diabetes, and obesity. These are risk factors for cardiovascular disease, which is the the foremost cause of global mortality (> 16.7 million deaths in 2003). Therefore, it is not surprising that orphan NRs and skeletal muscle are emerging as therapeutic candidates in the battle against dyslipidemia, diabetes, obesity, and cardiovascular disease.
Keyword Metabolism
Cardiovascular Disease
Cell Biology
Dominant-negative Mutations
Phosphatidylinositol 3-kinase Activity
Dependent Diabetes-mellitus
Uncoupling Protein-3 Gene
Causes Insulin-resistance
Pituitary-adrenal Axis
Q-Index Code C1

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 20 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 21 times in Scopus Article | Citations
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Created: Wed, 15 Aug 2007, 09:01:43 EST