No evidence of an additive inhibitory feeding effect following PP and PYY3−36 administration

Abstract

Pancreatic polypeptide (PP) and peptide YY (PYY) are released by the gut in response to nutrients and inhibit food intake in rodents and humans. We hypothesized that PP and PYY 3À36 would inhibit feeding additively. Fasted male C57BL/6 mice were injected intraperitoneally with saline, PP, PYY 3À36 or PP þ PYY 3À36 (n ¼ 7-10). Food intake at 1 h was significantly inhibited by 6 nmol kg À1 PP and by 6 nmol kg À1 PYY 3-36 (Po0.05) but not significantly following 3 nmol kg À1 PP þ 3 nmol kg À1 PYY 3À36 . In a higher dose study 30 nmol kg À1 PP, 30 nmol kg À1 PYY 3À36 and 30 nmol kg À1 PP þ 30 nmol kg À1 PYY 3À36 all inhibited 1 h food intake compared with saline (Po0.05) but there was no significant difference in the food intake of the combined group compared with either hormone individually. Subsequently, 16 fasted lean healthy human volunteers (6 men and 10 women) received, in random order, 90 min intravenous infusions of saline, 4 pmol kg À1 min À1 PP, 0.4 pmol kg À1 min À1 PYY 3À36 and 4 pmol kg À1 min À1 PP þ 0.4 pmol kg À1 min À1 PYY 3À36 . A pasta lunch was served 60 min following infusion. There was no evidence of a greater decrease in food intake with the combined PP þ PYY 3À36 treatment (buffet meal energy intake (KJ): saline 2633 ± 204, PP þ PYY 2693 ± 254, PP 2367 ± 199, PYY 2511 ± 196). These results suggest that PP and PYY 3À36 do not inhibit feeding additively in rodents or humans.

PYY3–36 and Oxyntomodulin Can Be Additive in Their Effect on Food Intake in Overweight and Obese Humans

“…However, studies performed on lean human volunteers do not always support this. Neary et al (30) reported that pancreatic polypeptide, a Y4 receptor agonist, and PYY 3–36 , a selective Y2 receptor agonist, did not reduce food intake when infused together. Others have found that, although cholecystokinin and glucagon-like peptide 1 (GLP-1) synergistically reduced hunger sensations, the combination did not reduce energy intake to a greater extent than infusion of either hormone separately (31).…”

Pancreatic Polypeptide Meal Response May Predict Gastric Band-Induced Weight Loss

“…Band adjustments occurred 2 days (mean, 49.4 h) prior to testing and were blinded to the subject and investigators. The mean time between paired tests was 4.5 days (range, [2][3][4][5][6][7][8][9][10][11][12][13][14], and no weight difference was found. Participants were asked to guess their band status after adjustment to assess blinding; 13 (76.5%) were undecided, three (17.5%) were correct and one was incorrect (6%).…”

“…Both have been associated with increased satiety in humans [3], and concentrations have been found to rise to a peak in direct proportion to the calorie content of a meal [1,2]. Administration of exogenous PP and PYY has both been shown to reduce food intake in rodents and humans, but their effects do not appear to be additive [4,5]. Some controversy exists regarding whether levels are lower or perhaps augmented in obesity [5,6].…”

Obesity treatment: novel peripheral targets

“…This gives rise to the hypothesis that treatment with multiple gut hormones could be better tolerated, and more effective, than single hormone treatment. Support for this hypothesis is available from small-scale studies of acute food intake in rodents and humans [99,116], although not all combinations have proven effective [209,210]. However, if nausea occurs not simply as a result of excessive satiety but also as a specific, independent side effect, it might be avoided, and weight loss maximized, by co-administration of non-nauseating doses of several hormones.…”