Submitted on June 26, 2007
Accepted on February 11, 2008
PYY3-36 injection in mice produces an acute anorexigenic effect followed by a delayed orexigenic effect not observed with other anorexigenic gut hormones
James Richard Parkinson1, Waljit Singh Dhillo1, Caroline J Small1, Owais B Chaudhri1, Gavin Bewick1, Iain Pritchard2, Stanley Moore2, Mohammed A. Ghatei3, and Stephen R. Bloom4*
1 Metabolic Medicine, Imperial College London, London, London, United Kingdom
2 Metabolic Medicine, Imperial College London, United Kingdom
3 United States; Metabolic Medicine, Imperial College London, London, London, United Kingdom
4 Division of Investigative Science, Imperial College at Hammersmith Campus, London, United Kingdom
* To whom correspondence should be addressed. E-mail: s.bloom{at}imperial.ac.uk.
Peptide YY (PYY) is secreted postprandially from the endocrine L-cells of the gastrointestinal tract. PYY3-36, the major circulating form of the peptide, is thought to reduce food intake in humans and rodents via high affinity binding to the auto-inhibitory NPY receptor, Y2R, within the arcuate nucleus (ARC). We studied the effect of early light phase injection of PYY3-36 on food intake in mice fasted for 0, 6, 12, 18, 24 and 30 hours and show that PYY3-36 produces an acute anorexigenic effect regardless of the duration of fasting. We also show evidence of a delayed orexigenic effect in ad libitum fed mice injected with PYY3-36 in the early light phase. This delayed orexigenic effect also occurs in mice administered a potent analogue of PYY3-36, D-Allo Ile3 PYY3-36, but not following injection of other anorectic agents; glucagon-like-peptide 1, oxyntomodulin and lithium chloride. Early light phase injection of PYY3-36 to ad libitum fed mice resulted in a trend towards increased levels of hypothalamic NPY and AgRP mRNA and a decrease in POMC mRNA at the beginning of the dark phase. Furthermore, plasma levels of ghrelin were significantly increased and there was a trend towards decreased plasma PYY3-36 levels at the beginning of the dark phase. These data indicate that PYY3-36 injection results in an acute anorexigenic effect followed by a delayed orexigenic effect.
