Possible mechanisms of circulating PYY-induced satiation in male rats

Peptide tyrosine-tyrosine (PYY) is implicated in eating control, but the site(s) and mechanism(s) of its action remain uncertain. We tested acute effects of intrameal hepatic portal vein (HPV) PYY(3-36) infusions on eating in adult, male rats and measured HPV and jugular vein (JV) plasma levels of PYY in response to a solid, mixed-nutrient meal. We also examined the effects of HPV PYY(3-36) infusions on JV plasma levels, flavor acceptance, and neuronal activation. Intrameal HPV PYY(3-36) infusions [1 and 3 nmol/kg body weight (BW)] selectively reduced (P < 0.05) ongoing meal size. HPV PYY levels increased (P < 0.05) during a chow (12.5 kcal) or an isocaloric high-fat meal. JV PYY levels were generally lower than HPV levels but also increased in response to the chow meal. HPV PYY(3-36) infusion (1 nmol/kg BW) caused a greater increase in JV PYY than a meal, but neither 1 nor 3 nmol/kg BW PYY(3-36) caused conditioned flavor avoidance. HPV PYY(3-36) (1 nmol/kg BW) increased the number of c-Fos-expressing cells in the nucleus tractus solitarii, the hypothalamic arcuate and paraventricular nuclei, the central area of the amygdala, and the nucleus accumbens but not in the area postrema and parabrachial nucleus. These data show that HPV infusions of PYY(3-36) inhibit eating in rats without causing avoidance, and they identify some brain areas that might be involved. Endogenous PYY may induce satiation by acting directly in the brain, but further studies should examine whether PYY(3-36) administrations that mimic the meal-induced increase in plasma PYY are sufficient to inhibit eating.