Source:http://linkedlifedata.com/resource/pubmed/id/19875640
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2009-12-23
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| pubmed:abstractText |
The present studies aimed to identify mechanisms contributing to amylin/leptin synergy in reducing body weight and adiposity. We reasoned that if amylin/leptin harnessed complementary neuronal pathways, then in the leptin-sensitive state, amylin should augment leptin signaling/binding and that in the absence of endogenous amylin, leptin signaling should be diminished. Amylin (50 microg/kg, ip) amplified low-dose leptin-stimulated (15 microg/kg, ip) phosphorylated signal transducer and activator of transcription-3 signaling within the arcuate nucleus (ARC) in lean rats. Amylin (50 microg/kg x d) or leptin (125 microg/kg x d) infusion to lean rats decreased 28-d food intake (14 and 10%, respectively), body weight (amylin by 4.3%, leptin by 4.9%), and epididymal fat (amylin by 19%, leptin by 37%). Amylin/leptin co-infusion additively decreased food intake (by 26%) and reduced body weight (by 15%) and epididymal fat (by 78%; all P < 0.05 vs. all groups) in a greater than mathematically additive manner, consistent with synergy. Amylin increased leptin binding within the ventromedial hypothalamus (VMN) by 35% and dorsomedial hypothalamus by 47% (both P < 0.05 vs. vehicle). Amylin/leptin similarly increased leptin binding in the VMN by 40% and ARC by 70% (P < 0.05 vs. vehicle). In amylin-deficient mice, hypothalamic leptin receptor mRNA expression was reduced by 50%, leptin-stimulated phosphorylated signal transducer and activator of transcription-3 within ARC and VMN was reduced by 40%, and responsiveness to leptin's (1 mg/kg x d for 28 d) weight-reducing effects was attenuated (all P < 0.05 vs. wild-type controls). We suggest that amylin/leptin's marked weight- and fat-reducing effects are due to activation of intrinsic synergistic neuronal signaling pathways and further point to the integrated neurohormonal therapeutic potential of amylin/leptin agonism in obesity.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid,
http://linkedlifedata.com/resource/pubmed/chemical/Islet Amyloid Polypeptide,
http://linkedlifedata.com/resource/pubmed/chemical/Leptin,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
1945-7170
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| pubmed:author |
pubmed-author:Dunn-MeynellAmbrose AAA,
pubmed-author:GriffinPeter SPS,
pubmed-author:GuGuibaoG,
pubmed-author:IraniBomanB,
pubmed-author:LevinBarry EBE,
pubmed-author:ParkesDavid GDG,
pubmed-author:RothJonathan DJD,
pubmed-author:TrevaskisJames LJL,
pubmed-author:TurekVictoria FVF,
pubmed-author:VuCalvinC,
pubmed-author:WittmerCarrieC
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| pubmed:issnType |
Electronic
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| pubmed:volume |
151
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
143-52
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:19875640-Amyloid,
pubmed-meshheading:19875640-Animals,
pubmed-meshheading:19875640-Arcuate Nucleus,
pubmed-meshheading:19875640-Area Postrema,
pubmed-meshheading:19875640-Drug Synergism,
pubmed-meshheading:19875640-Female,
pubmed-meshheading:19875640-Islet Amyloid Polypeptide,
pubmed-meshheading:19875640-Leptin,
pubmed-meshheading:19875640-Male,
pubmed-meshheading:19875640-Mice,
pubmed-meshheading:19875640-Mice, Inbred C57BL,
pubmed-meshheading:19875640-Mice, Knockout,
pubmed-meshheading:19875640-Models, Animal,
pubmed-meshheading:19875640-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:19875640-Rats,
pubmed-meshheading:19875640-Rats, Sprague-Dawley,
pubmed-meshheading:19875640-Rodentia,
pubmed-meshheading:19875640-STAT3 Transcription Factor,
pubmed-meshheading:19875640-Signal Transduction
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| pubmed:year |
2010
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| pubmed:articleTitle |
Mechanisms of amylin/leptin synergy in rodent models.
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| pubmed:affiliation |
Amylin Pharmaceuticals, Inc., 9360 Towne Centre Drive, San Diego, California 92121, USA.
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| pubmed:publicationType |
Journal Article
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