Effects of PYY_3–36 and GLP-1 on energy intake, energy expenditure, and appetite in overweight men

Abstract

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.

Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx

“…Stimulating secretion of (endogenous) NT may turn out to be a beneficial therapeutic target, as agents capable of this might also stimulate secretion of other anorectic hormones from cells sharing similar secretory sensors (in particular CCK, GLP-1, and oxyntomodulin); such agents would be expected to have pronounced effects on appetite because of potentiating interactions (25). Our findings suggest that NT secretion should always be considered in studies of appetite inhibition by carbohydrate-containing meals.…”

Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance

“…Several P-CR weight-loss intervention studies and reviews have consistently reported a higher protein component of solid food or drink induces greater satiety and delay appetite sensations at later meals than other macronutrients [9,44,45,46]. Although no differences were noted in hunger ratings during the current WM phase, in a recent meta-analysis, higher protein preloads were found to increase fullness ratings more than lower protein preloads under tightly controlled conditions [47].…”

“…Although no differences were noted in hunger ratings during the current WM phase, in a recent meta-analysis, higher protein preloads were found to increase fullness ratings more than lower protein preloads under tightly controlled conditions [47]. This macronutrient-specific effect is mediated by gut hormones regulating satiety, such as GLP-1, CCK, and PYY [9,44,45,46]. It is likely the 1 or 2 days/month of IF provided an additive role in facilitating the WL maintenance mP-CR, which may be an interesting area for future studies.…”

In vivo and in vitro degradation of peptide YY3–36 to inactive peptide YY3–34 in humans

“…Anorexigenic effects of PYY have been demonstrated in several studies with intravenous administration of PYY (6,16,32,34), whereas infusions of PYY have no effect on food intake (34), suggesting that the cleavage of PYY to PYY is not as complete and rapid as for GLP-1 (34). The half-life of PYY has been determined as 9.1 min (5).…”