Document Detail

Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene.
MedLine Citation:
PMID:  20367758     Owner:  NLM     Status:  MEDLINE    
Many vertebrates express profound annual cycles of body fattening, although it is not clear whether these represent differential activity of the central pathways known to mediate homeostatic control of food intake and energy expenditure, or whether the recent discovery of a major role for pars tuberalis-ependymal signalling points towards novel mechanisms. We examined this in the Siberian hamster (Phodopus sungorus) by using gene transfection to up-regulate a major orexigenic peptide, agouti-related peptide (AgRP), and then determined whether this increased anabolic drive could prevent the short-day induced winter catabolic state. Infusions of a recombinant adeno-associated virus encoding an AgRP construct into the hypothalamus of hamsters in the long-day obese phase of their seasonal cycle produced a 20% gain in body weight over 6 weeks compared to hamsters receiving a control reporter construct, reflecting a significant increase in food intake and a significant decrease in energy expenditure. However, all hamsters showed a significant, prolonged decrease in body weight when exposed to short photoperiods, despite the hamsters expressing the AgRP construct maintaining a higher food intake and lower energy expenditure relative to the control hamsters. Visualisation of the green fluorescent protein reporter and analysis of AgRP-immunoreactivity confirmed widespread expression of the construct in the hypothalamus, which was maintained for the 21-week duration of the study. In conclusion, the over-expression of AgRP in the hypothalamus produced a profoundly obese state but did not block the seasonal catabolic response, suggesting a separation of rheostatic mechanisms in seasonality from those maintaining homeostasis of energy metabolism.
P H Jethwa; A Warner; M J Fowler; M Murphy; M W de Backer; R A H Adan; P Barrett; J M Brameld; F J P Ebling
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-27
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  22     ISSN:  1365-2826     ISO Abbreviation:  J. Neuroendocrinol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-29     Completed Date:  2010-11-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  564-75     Citation Subset:  IM    
School of Biomedical Sciences, University of Nottingham Medical School, Queens Medical Centre, Nottingham, UK.
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MeSH Terms
Agouti-Related Protein / genetics*
Base Sequence
Circadian Rhythm*
DNA Primers
Dependovirus / genetics
Genetic Vectors
Green Fluorescent Proteins / genetics
Microscopy, Fluorescence
Polymerase Chain Reaction
Weight Loss*
Grant Support
BB/E020437/1//Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Agouti-Related Protein; 0/DNA Primers; 147336-22-9/Green Fluorescent Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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