Linked Life Data

11830271

Source:http://linkedlifedata.com/resource/pubmed/id/11830271

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2002-2-6
pubmed:abstractText
Orexins (forms A and B) belong to a new family of peptides that, as neuropeptide Y (NPY), stimulate food intake when centrally injected. The ob/ob mouse is a well-characterized model of hyperphagia and obesity associated with strong metabolic disturbances and a central dysregulation of peptides involved in the control of feeding. In the present report, we investigated the hypocretin (Hcrt)/orexin (OX) peptide pathway in lean and ob/ob mice. Prepro-Hcrt/OX mRNA expression, measured by in situ hybridization was restricted to the lateral hypothalamus area. It was significantly decreased in ob/ob mice (-18%; p<0.01). When estimated by real time RT-PCR in the whole hypothalamus, this decrease amounted to 65% (p<0.001). Hcrt-1/OX-A peptide concentrations, measured by RIA in microdissected hypothalamic nuclei were high in the lateral hypothalamus (LH) and lower in the arcuate (ARC) and paraventricular nuclei (PVN). In ob/ob mice, OX-A levels were significantly lower than in lean mice in the LH (-34%; p<0.02) and in the PVN (-72%; p<0.005). Acute intracerebroventricular injection of Hcrt-1/OX-A (1-10 nmol) stimulated feeding in lean, but not in ob/ob mice, whereas Hcrt-2/OX-B (1-10 nmol) had the opposite effect. Acute third ventricle (i3vt) injections of Hcrt/OX peptides in ob/ob mice transiently increased their metabolic rate and stimulated lipid substrate utilization. These findings provide direct evidence that Hcrt/OX peptides are down-regulated in the hypothalamus of ob/ob mice, contrary to the NPY system. The present data argues that Hcrt/OX peptides are not primarily responsible for the metabolic syndrome of the ob/ob mice. The diminution in the OX tone might participate in a counterregulatory system necessary to limit the adverse effects of NPY on food intake and body weight.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0167-0115
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11-20
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11830271-Animals, pubmed-meshheading:11830271-Carrier Proteins, pubmed-meshheading:11830271-Eating, pubmed-meshheading:11830271-Energy Metabolism, pubmed-meshheading:11830271-Feeding Behavior, pubmed-meshheading:11830271-Gene Expression, pubmed-meshheading:11830271-Hypothalamic Area, Lateral, pubmed-meshheading:11830271-In Situ Hybridization, pubmed-meshheading:11830271-Injections, Intraventricular, pubmed-meshheading:11830271-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:11830271-Male, pubmed-meshheading:11830271-Mice, pubmed-meshheading:11830271-Mice, Inbred C57BL, pubmed-meshheading:11830271-Mice, Inbred Strains, pubmed-meshheading:11830271-Neuropeptide Y, pubmed-meshheading:11830271-Neuropeptides, pubmed-meshheading:11830271-Obesity, pubmed-meshheading:11830271-RNA, Messenger, pubmed-meshheading:11830271-Radioimmunoassay, pubmed-meshheading:11830271-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2002
pubmed:articleTitle
Orexins/hypocretins in the ob/ob mouse: hypothalamic gene expression, peptide content and metabolic effects.
pubmed:affiliation
Metabolic Diseases Physiology Department, Millennium Pharmaceuticals 75 Sidney Street, MA 02139, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't