Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2004-8-23
pubmed:abstractText
The staggerer mice carry a deletion in the RORalpha gene and have a prolonged humoral response, overproduce inflammatory cytokines, and are immunodeficient. Furthermore, the staggerer mice display lowered plasma apoA-I/-II, decreased plasma high density lipoprotein cholesterol and triglycerides, and develop hypo-alpha-lipoproteinemia and atherosclerosis. However, relatively little is known about RORalpha in the context of target tissues, target genes, and lipid homeostasis. For example, RORalpha is abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for approximately 40% of total body weight and 50% of energy expenditure. This lean tissue is a primary site of glucose disposal and fatty acid oxidation. Consequently, muscle has a significant role in insulin sensitivity, obesity, and the blood-lipid profile. In particular, the role of RORalpha in skeletal muscle metabolism has not been investigated, and the contribution of skeletal muscle to the ROR-/- phenotype has not been resolved. We utilize ectopic dominant negative RORalpha expression in skeletal muscle cells to understand the regulatory role of RORs in this major mass peripheral tissue. Exogenous dominant negative RORalpha expression in skeletal muscle cells represses the endogenous levels of RORalpha and -gamma mRNAs and ROR-dependent gene expression. Moreover, we observed attenuated expression of many genes involved in lipid homeostasis. Furthermore, we show that the muscle carnitine palmitoyltransferase-1 and caveolin-3 promoters are directly regulated by ROR and coactivated by p300 and PGC-1. This study implicates RORs in the control of lipid homeostasis in skeletal muscle. In conclusion, we speculate that ROR agonists would increase fatty acid catabolism in muscle and suggest selective activators of ROR may have therapeutic utility in the treatment of obesity and atherosclerosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Carnitine O-Palmitoyltransferase, http://linkedlifedata.com/resource/pubmed/chemical/Cav3 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Caveolin 3, http://linkedlifedata.com/resource/pubmed/chemical/Caveolins, http://linkedlifedata.com/resource/pubmed/chemical/E1A-Associated p300 Protein, http://linkedlifedata.com/resource/pubmed/chemical/Ep300 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Glucose, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 1..., http://linkedlifedata.com/resource/pubmed/chemical/RNA, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/RORA protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/peroxisome-proliferator-activated...
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
36828-40
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15199055-Animals, pubmed-meshheading:15199055-Arteriosclerosis, pubmed-meshheading:15199055-COS Cells, pubmed-meshheading:15199055-Carnitine O-Palmitoyltransferase, pubmed-meshheading:15199055-Caveolin 3, pubmed-meshheading:15199055-Caveolins, pubmed-meshheading:15199055-Cell Differentiation, pubmed-meshheading:15199055-Cell Division, pubmed-meshheading:15199055-Cell Line, pubmed-meshheading:15199055-E1A-Associated p300 Protein, pubmed-meshheading:15199055-Gene Expression Regulation, pubmed-meshheading:15199055-Genes, Dominant, pubmed-meshheading:15199055-Glucose, pubmed-meshheading:15199055-Glutathione Transferase, pubmed-meshheading:15199055-Humans, pubmed-meshheading:15199055-Lipid Metabolism, pubmed-meshheading:15199055-Mice, pubmed-meshheading:15199055-Muscle, Skeletal, pubmed-meshheading:15199055-Mutagenesis, Site-Directed, pubmed-meshheading:15199055-Nuclear Proteins, pubmed-meshheading:15199055-Nuclear Receptor Subfamily 1, Group F, Member 1, pubmed-meshheading:15199055-Obesity, pubmed-meshheading:15199055-Phenotype, pubmed-meshheading:15199055-Plasmids, pubmed-meshheading:15199055-Promoter Regions, Genetic, pubmed-meshheading:15199055-RNA, pubmed-meshheading:15199055-RNA, Messenger, pubmed-meshheading:15199055-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:15199055-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15199055-Trans-Activators, pubmed-meshheading:15199055-Transcription Factors, pubmed-meshheading:15199055-Transfection
pubmed:year
2004
pubmed:articleTitle
RORalpha regulates the expression of genes involved in lipid homeostasis in skeletal muscle cells: caveolin-3 and CPT-1 are direct targets of ROR.
pubmed:affiliation
Institute for Molecular Bioscience, Division of Molecular Genetics and Development, School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't