PYY is secreted postprandially from the endocrine L-cells of the gastrointestinal tract. PYY336, 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 PYY336; (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 PYY336 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 PYY336 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 PYY336 produced a significant reduction in FI regardless of the duration of fasting [0 h fasted group, 24 h FI: Saline: 0.13±0.02 g, PYY336: 0.06±0.01 g, (P<0.05 vs. Saline); 6 h fasted group, 12 h FI: Saline: 1.7±0.02 g, PYY336: 0.05±0.01 g, (P<0.001 vs. Saline)].
(2) Early light phase injection of PYY336 caused an increase in night-time feeding [1224 h FI: Saline: 3.1±0.07 g; PYY336: 3.43±0.08 g, (P<0.01 vs. Saline)]. There was no change in FI or metabolic parameters in the 012 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 PYY336. (2) PYY336 causes a delayed orexigenic effect not seen with other peripherally administered anorexigenic gut hormones.