Linked Life Data

19617349

Source:http://linkedlifedata.com/resource/pubmed/id/19617349

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
38
pubmed:dateCreated
2009-9-14
pubmed:abstractText
Obesity and type 2 diabetes are related metabolic disorders of high prevalence. The constitutive androstane receptor (CAR) was initially characterized as a xenobiotic receptor regulating the responses of mammals to xenotoxicants. In this study, we have uncovered an unexpected role of CAR in preventing obesity and alleviating type 2 diabetes. Using a high fat diet (HFD)-induced obesity model, we showed that treatment of wild type mice with the CAR agonist 1,4-bis[2-(3,5 dichloropyridyloxy)] benzene (TCPOBOP) efficiently prevented obesity from happening or reversed preinduced obesity. Treatment with TCPOBOP improved insulin sensitivity in both the HFD-induced type 2 diabetic model and the ob/ob mice. In contrast, CAR null mice maintained on a chow diet showed spontaneous insulin insensitivity, which cannot be relieved by TOPOBOP treatment. The hepatic steatosis in HFD-treated mice and ob/ob mice was markedly reduced by the TCPOBOP treatment. The metabolic benefits of CAR activation may have resulted from the combined effect of inhibition of lipogenesis, very low density lipoprotein secretion and export of triglycerides, and gluconeogenesis as well as increases in brown adipose tissue energy expenditure and peripheral fat mobilization. Moreover, the skeletal muscle of CAR-activated mice showed a decreased incomplete oxidation, despite having a lower expression level of peroxisome proliferator-activated receptor alpha and its target genes involved in fatty acid oxidation. In summary, our results have revealed an important metabolic function of CAR and may establish this "xenobiotic receptor" as a novel therapeutic target for the prevention and treatment of obesity and type 2 diabetes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25984-92
pubmed:dateRevised
2010-9-21
pubmed:meshHeading
pubmed-meshheading:19617349-Adipose Tissue, pubmed-meshheading:19617349-Animals, pubmed-meshheading:19617349-Diabetes Mellitus, Type 2, pubmed-meshheading:19617349-Diet, pubmed-meshheading:19617349-Dietary Fats, pubmed-meshheading:19617349-Disease Models, Animal, pubmed-meshheading:19617349-Energy Metabolism, pubmed-meshheading:19617349-Fatty Acids, pubmed-meshheading:19617349-Fatty Liver, pubmed-meshheading:19617349-Gluconeogenesis, pubmed-meshheading:19617349-Humans, pubmed-meshheading:19617349-Insulin Resistance, pubmed-meshheading:19617349-Lipoproteins, VLDL, pubmed-meshheading:19617349-Mice, pubmed-meshheading:19617349-Mice, Knockout, pubmed-meshheading:19617349-Muscle, Skeletal, pubmed-meshheading:19617349-Obesity, pubmed-meshheading:19617349-Oxidation-Reduction, pubmed-meshheading:19617349-PPAR alpha, pubmed-meshheading:19617349-Pyridines, pubmed-meshheading:19617349-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:19617349-Triglycerides
pubmed:year
2009
pubmed:articleTitle
The constitutive androstane receptor is an anti-obesity nuclear receptor that improves insulin sensitivity.
pubmed:affiliation
Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural