Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene

Preeti H Jethwa, Amy Warner, Maxine J Fowler, Michelle Murphy, Marijke W de Backer, Roger A H Adan, Perry Barrett, John M Brameld, Francis J P Ebling

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Many vertebrates express profound annual cycles of body fattening, but 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 upregulate a major orexigenic peptide, agouti-related peptide (AgRP), then determining 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 six weeks as 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 GFP 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.
Original languageEnglish
Pages (from-to)564-575
Number of pages12
JournalJournal of Neuroendocrinology
Volume22
Issue number6
Early online date27 Mar 2010
DOIs
Publication statusPublished - Jun 2010

Fingerprint

Phodopus
Weight Loss
Cricetinae
Energy Metabolism
Peptides
Genes
Hypothalamus
Eating
Body Weight
Dependovirus
Photoperiod
Transfection
Vertebrates
Dasyproctidae
Homeostasis
Up-Regulation

Keywords

  • AgRP
  • body weight
  • appetite
  • metabolic rate

Cite this

Jethwa, P. H., Warner, A., Fowler, M. J., Murphy, M., de Backer, M. W., Adan, R. A. H., ... Ebling, F. J. P. (2010). Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene. Journal of Neuroendocrinology, 22(6), 564-575. https://doi.org/10.1111/j.1365-2826.2010.02001.x

Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene. / Jethwa, Preeti H; Warner, Amy; Fowler, Maxine J; Murphy, Michelle; de Backer, Marijke W; Adan, Roger A H; Barrett, Perry; Brameld, John M; Ebling, Francis J P.

In: Journal of Neuroendocrinology, Vol. 22, No. 6, 06.2010, p. 564-575.

Research output: Contribution to journalArticle

Jethwa, PH, Warner, A, Fowler, MJ, Murphy, M, de Backer, MW, Adan, RAH, Barrett, P, Brameld, JM & Ebling, FJP 2010, 'Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene', Journal of Neuroendocrinology, vol. 22, no. 6, pp. 564-575. https://doi.org/10.1111/j.1365-2826.2010.02001.x
Jethwa, Preeti H ; Warner, Amy ; Fowler, Maxine J ; Murphy, Michelle ; de Backer, Marijke W ; Adan, Roger A H ; Barrett, Perry ; Brameld, John M ; Ebling, Francis J P. / Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene. In: Journal of Neuroendocrinology. 2010 ; Vol. 22, No. 6. pp. 564-575.
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