Peptide YY3–36-induced inhibition of food intake in female monkeys

Abstract: Peptide YY (PYY) is produced in L cells of the intestine and is released after eating. PYY circulates in a truncated form designated PYY3–36. PYY3–36 is thought to be a physiologic anorexigenic peptide. The objective of the current study was to test the effect of exogenous PYY3–36 on food intake in non-human primates exposed to different ovarian steroid milieus. The study was conducted in four ovariectomized cynomolgus monkeys replaced with estrogen alone for 2 weeks followed by estrogen in combination with progesterone for 2 weeks to mimic the menstrual cycle. The effect of PYY3–36 on food intake was tested during each week of the simulated menstrual cycle by comparing the 2 h food intake following intracerebroventricular (icv) injection of artificial cerebrospinal fluid (aCSF) or PYY3–36. Despite considerable variation in food intake following aCSF, PYY3–36 consistently inhibited food consumption, except during week 2 of estrogen plus progesterone replacement. PYY3–36 reduced food consumption by 16.2 g (95% confidence interval (CI)=4.5–27.9 g) and 26.6 g (95% CI=7.3–45.9 g) in weeks 1 and 2 respectively of estrogen only treatment and by 38.2 g (95% CI=26.1–50.2 g) in week 1 of estrogen plus progesterone treatment. In contrast, PYY3–36 injected in week 2 of estrogen plus progesterone did not consistently inhibit food intake (13.1 g; CI=−49.5–75.7). This is the first study to report the effect of PYY3–36 on food consumption in female monkeys. We conclude that icv administration of PYY3–36 has a strong anorexic effect in female cynomolgus monkeys and that sensitivity to PYY3–36 may be influenced by the ovarian steroid milieu. [Copyright &y& Elsevier]