Hepatic portal vein (HPV) peptide tyrosine-tyrosine (PYY) and meal-taking in rats

Abstract

Peripheral administration of PYY inhibits eating, but the site, mechanism, and physiological relevance of PYY's eating-inhibitory action are unclear. Here we equipped adult male rats (n = 8) kept on a medium-fat diet with HPV catheters and infused (0.2 ml/min) glucagon-like peptide-1 (GLP-1), PYY (1.0 nmol/kg BW, each) or vehicle (V) by remote control during the first spontaneous nocturnal meal. Either peptide reduced (p < 0.05) ongoing meal size (V: 4.1 ± 0.2, PYY: 2.4 ± 0.2, GLP-1: 1.6 ± 0.1 g; mean ± SEM). Subsequent meal sizes and cumulative food intake (2 h and beyond) were unaffected. In 10 other rats kept on chow intra-meal HPV PYY (1.0 and 3.0 nmol/kg BW) infusions also reduced (p < 0.05) meal size (V: 2.6 ± 0.2, 0.33 nmol: 2.5 ± 0.4, 1.0 nmol: 1.8 ± 0.2, 3 nmol: 1.8 ± 0.2 g). Intragastric nutrient infusions usually stimulate intestinal PYY release, but so far circulating PYY has not been measured in relation to real meals in rats. We did so and found that an isocaloric chow or high fat (HF) meal (12.5 kcal) given at dark onset after 3 h food deprivation increased (p < 0.05) HPV plasma PYY concentration from 70 ± 6 (0 min) to 104 ± 9 pg/ml (chow) and from 56 ± 9 (0 min) to 85 ± 9 pg/ml (HF) at 15 min after meal onset. Plasma PYY did not increase under control conditions without a meal. These findings show that HPV PYY increases during normal meals in rats and that experimentally induced prandial increases in HPV PYY can acutely inhibit eating. Further studies should examine whether PYY administrations that mimic the meal-induced increase are sufficient to inhibit eating.