Linked Life Data

16728530

Source:http://linkedlifedata.com/resource/pubmed/id/16728530

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2006-9-27
pubmed:abstractText
Single-minded 1 (SIM1) is one of only six genes implicated in human monogenic obesity. Haploinsufficiency of this hypothalamic transcription factor is associated with hyperphagic obesity and increased linear growth in both humans and mice. Additionally, Sim1 heterozygous mice show enhanced hyperphagia and obesity in response to a high-fat diet. Thus the phenotype of Sim1 haploinsufficiency is similar to that of agouti yellow (Ay), and melanocortin 4 receptor (Mc4r) knockout mice, both of which are defective in hypothalamic melanocortin signaling. Sim1 and Mc4r are both expressed in the paraventricular nucleus (PVN). Here we report that Sim1 heterozygous mice, which have normal energy expenditure, are hyperphagic despite having elevated hypothalamic proopiomelanocortin (Pomc) expression. In response to the melanocortin agonist melanotan-2 (MTII) they exhibit a blunted suppression of feeding yet increase their energy expenditure normally. They also fail to activate PVN neurons in response to the drug at a dose that induces robust c-Fos expression in a subset of Sim1 PVN neurons in wild-type mice. The resistance to melanocortin signaling in Sim1 heterozygotes is not due to a reduced number of Sim1 neurons in the PVN. Hypothalamic Sim1 gene expression is induced by leptin and MTII treatment. Our results demonstrate that Sim1 heterozygotes are resistant to hypothalamic melanocortin signaling and suggest that Sim1-expressing PVN neurons regulate feeding, but not energy expenditure, in response to melanocortin signaling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2483-92
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:16728530-Animals, pubmed-meshheading:16728530-Anorexia, pubmed-meshheading:16728530-Basic Helix-Loop-Helix Transcription Factors, pubmed-meshheading:16728530-DNA Primers, pubmed-meshheading:16728530-Feeding Behavior, pubmed-meshheading:16728530-Gene Expression Regulation, pubmed-meshheading:16728530-Heterozygote, pubmed-meshheading:16728530-Immunohistochemistry, pubmed-meshheading:16728530-Mice, pubmed-meshheading:16728530-Mice, Inbred C57BL, pubmed-meshheading:16728530-Models, Biological, pubmed-meshheading:16728530-Paraventricular Hypothalamic Nucleus, pubmed-meshheading:16728530-Peptides, Cyclic, pubmed-meshheading:16728530-Pro-Opiomelanocortin, pubmed-meshheading:16728530-Repressor Proteins, pubmed-meshheading:16728530-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16728530-Signal Transduction, pubmed-meshheading:16728530-alpha-MSH
pubmed:year
2006
pubmed:articleTitle
Sim1 haploinsufficiency impairs melanocortin-mediated anorexia and activation of paraventricular nucleus neurons.
pubmed:affiliation
Department of Pediatrics, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8591, USA. bassil.kublaoui@utsouthwestern.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural