Linked Life Data

12582458

Source:http://linkedlifedata.com/resource/pubmed/id/12582458

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2003-2-12
pubmed:abstractText
The recent rapid rise in the incidence of obesity has prompted investigations into understanding the hormonal and neuronal pathways involved in body weight homeostasis in order to devise novel therapeutic strategies. The early enthusiasm for the adipocyte hormone leptin as a regulator of fat mass was largely discarded because of the apparent development of leptin resistance, as seen in obese subjects with elevated blood leptin levels. We postulated that this leptin ineffectiveness may be caused by a lack of leptin availability at target sites in the hypothalamus. To test this hypothesis, we used viral vectors to introduce the leptin gene into the brain for a sustained supply of leptin in the hypothalamus. A single injection of recombinant adeno-associated virus encoding the leptin gene (rAAV-lep) into the third cerebroventricle prevented the aging-associated gradual increase in body weight and adiposity in adult rats for 6 months of the experiment. When administered to prepubertal rats, significantly lower body weight gain and adiposity were maintained for up to 10 months of the experiment. In addition, obesity was prevented in rats introduced to a high-fat diet and also reversed in obese-prone rats maintained on a high-fat diet. Body weight homeostasis and loss of adiposity by leptin gene therapy was achieved by an increase in energy expenditure, and when the rAAV-lep titer was increased, there was also a voluntary reduction in food intake. Importantly, this therapy reduced blood levels of insulin, triglycerides and free fatty acids, the pathophysiologic correlates of the metabolic syndrome. Thus, the long-term beneficial effects of central leptin gene therapy may herald the development of newer therapeutic strategies to control the epidemic of obesity and related metabolic disorders.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1699-3993
pubmed:author
pubmed:copyrightInfo
(c) 2002 Prous Science. Allrights reserved.
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
745-57
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Obesity and metabolic syndrome: long-term benefits of central leptin gene therapy.
pubmed:affiliation
Department of Physiology and Functional Genomics, University of Florida College of Medicine, McKnight Brain Institute, PO Box 100274, Gainesville, FL 32610-0274, U.S.A. pkalra@phys.med.ufl.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review