Effects of PYY3-36 and GLP-1 on energy intake, energy expenditure, and appetite in overweight men.

Our aim was to examine the effects of GLP-1 and PYY3-36, separately and in combination, on energy intake, energy expenditure, appetite sensations, glucose and fat metabolism, ghrelin, and vital signs in healthy overweight men. Twenty-five healthy male subjects participated in this randomized, double-blinded, placebo-controlled, four-arm crossover study (BMI 29 ± 3 kg/m(2), age 33 ± 9 yr). On separate days they received a 150-min intravenous infusion of 1) 0.8 pmol·kg(-1)·min(-1) PYY3-36, 2) 1.0 pmol·kg(-1)·min(-1) GLP-1, 3) GLP-1 + PYY3-36, or 4) placebo. Ad libitum energy intake was assessed during the final 30 min. Measurements of appetite sensations, energy expenditure and fat oxidation, vital signs, and blood variables were collected throughout the infusion period. No effect on energy intake was found after monoinfusions of PYY3-36 (-4.2 ± 4.8%, P = 0.8) or GLP-1 (-3.0 ± 4.5%, P = 0.9). However, the coinfusion reduced energy intake compared with placebo (-30.4 ± 6.5%, P < 0.0001) and more than the sum of the monoinfusions (P < 0.001), demonstrating a synergistic effect. Coinfusion slightly increased sensation of nausea (P < 0.05), but this effect could not explain the effect on energy intake. A decrease in plasma ghrelin was found after all treatments compared with placebo (all P < 0.05); however, infusions of GLP-1 + PYY3-36 resulted in an additional decrease compared with the monoinfusions (both P < 0.01). We conclude that coinfusion of GLP-1 and PYY3-36 exerted a synergistic effect on energy intake. The satiating effect of the meal was enhanced by GLP-1 and PYY3-36 in combination compared with placebo. Coinfusion was accompanied by slightly increased nausea and a decrease in plasma ghrelin, but neither of these factors could explain the reduction in energy intake.