Linked Life Data

17430219

Source:http://linkedlifedata.com/resource/pubmed/id/17430219

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-4-13
pubmed:abstractText
Obesity and metabolic syndrome are increasing dramatically worldwide, contributing to cardiovascular morbidity and mortality. There are currently few safe and efficacious therapeutics for obesity and most strategies are focused on appetite suppression. Thyroid hormones reduce adiposity via increased metabolic rate, but unfortunately they cause large changes in metabolic rate and direct cardiac acceleration, making them useless for treating obesity. Thyroid hormone receptors (TRs) work as transcription factors and two subtypes exist: TRalpha and TRbeta. TRalpha mediates tachycardia and much of the metabolic rate effect, while TRbeta mediates cholesterol and TSH lowering effects of thyroid hormones. TRbeta activation modestly increases metabolic rate such that a therapeutic window of 5-10 fold increases in metabolic rate can be seen without tachycardia. This was initially studied in TRalpha(1)(-/-) mice. Recent structure activity work has resulted in the discovery of several TRbeta selective thyromimetics such as KB-141. Studies with KB-141 show that it has a 10-fold window in which therapeutic increases in metabolic rate are seen without tachycardia or cardiac hypertrophy. This agent lowers cholesterol in rats and primates. In primates, KB-141 causes significant weight and cholesterol reduction in addition to the independent risk factor Lp(a). These effects were seen without any effect on heart rate, unlike thyroid hormone (T(3)). Further work with TRbeta selective agents is warranted and recent work suggests the possibility of developing compounds that selectively penetrate different tissues which may have an even more desirable therapeutic window. Selective thyromimetics, therefore, may be useful as adjunctive therapy to appetite suppressants along with exercise and diet restriction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1570-1611
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
141-54
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Therapeutic potential for thyroid hormone receptor-beta selective agonists for treating obesity, hyperlipidemia and diabetes.
pubmed:affiliation
Department of Pharmacology, Eurofins Scientific-PSL, 2394 Rt. 130, Dayton, NJ 08810, USA. garygrover@productsafetylabs.com
pubmed:publicationType
Journal Article, Review