Linked Life Data

21048120

Source:http://linkedlifedata.com/resource/pubmed/id/21048120

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
44
pubmed:dateCreated
2010-11-4
pubmed:abstractText
D-Fenfluramine (D-Fen) increases serotonin (5-HT) content in the synaptic cleft and exerts anorexigenic effects in animals and humans. However, the neural circuits that mediate these effects are not fully identified. To address this issue, we assessed the efficacy of D-Fen-induced hypophagia in mouse models with manipulations of several genes in selective populations of neurons. Expectedly, we found that global deletion of 5-HT 2C receptors (5-HT(2C)Rs) significantly attenuated D-Fen-induced anorexia. These anorexigenic effects were restored in mice with 5-HT(2C)Rs expressed only in pro-opiomelanocortin (POMC) neurons. Further, we found that deletion of melanocortin 4 receptors (MC4Rs), a downstream target of POMC neurons, abolished anorexigenic effects of D-Fen. Reexpression of MC4Rs only in SIM1 neurons in the hypothalamic paraventricular nucleus and neurons in the amygdala was sufficient to restore the hypophagic property of D-Fen. Thus, our results identify a neurochemically defined neural circuit through which D-Fen influences appetite and thereby indicate that this 5-HT(2C)R/POMC-MC4R/SIM1 circuit may yield a more refined target to exploit for weight loss.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14630-4
pubmed:dateRevised
2011-3-10
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
A serotonin and melanocortin circuit mediates D-fenfluramine anorexia.
pubmed:affiliation
Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural