Endocrine Abstracts (2007) 13 P236

PYY3–36 produces an acute anorexigenic effect followed by a later orexigenic effect not seen with other anorexigenic peptides

James Parkinson, Waljit Dhillo, Caroline Small, Mohammed Ghatei & Stephen Bloom

Imperial College, London, United Kingdom.

PYY is secreted postprandially from the endocrine L-cells of the gastrointestinal tract. PYY3–36, the major circulating form of PYY, reduces food intake in humans and rodents via high affinity binding to the auto-inhibitory NPY receptor, Y2R, within the hypothalamic arcuate nucleus.

Aims: To investigate (1) the effects of length of fast on the anorexigenic actions of PYY3–36; (2) the effects of early light phase administration of gut hormones on subsequent dark phase food intake (FI).

Methods: (1) C57BL/6 mice were administered PYY3–36 by intraperitoneal injection following fasting for 0, 6, 12, 18, 24 and 30 hours and FI measured.

(2) C57BL/6 mice were maintained in CLAMS metabolic cages under a 12 h light-dark cycle. Intraperitoneal injection of PYY3–36 or saline at lights-on (0800 h) was followed by fasting for 4 h and measurement of FI, CO2 production and oxygen consumption for 24 h.

(3) C57BL/6 mice were administered OXM, GLP-1 or saline, intraperitoneally at lights-on followed by a 4 h fast and measurement of FI for 24 h

Results: (1) Peripheral PYY3–36 produced a significant reduction in FI regardless of the duration of fasting [0 h fasted group, 2–4 h FI: Saline: 0.13±0.02 g, PYY3–36: 0.06±0.01 g, (P<0.05 vs. Saline); 6 h fasted group, 1–2 h FI: Saline: 1.7±0.02 g, PYY3–36: 0.05±0.01 g, (P<0.001 vs. Saline)].

(2) Early light phase injection of PYY3–36 caused an increase in night-time feeding [12–24 h FI: Saline: 3.1±0.07 g; PYY3–36: 3.43±0.08 g, (P<0.01 vs. Saline)]. There was no change in FI or metabolic parameters in the 0–12 h period leading up to lights out.

(3) GLP-1 and OXM had no effect on night-time FI.

Conclusions: These novel findings suggest that (1) Length of fasting does not significantly alter the anorexigenic effects of PYY3–36. (2) PYY3–36 causes a delayed orexigenic effect not seen with other peripherally administered anorexigenic gut hormones.

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