Abstract
Background:Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment of obesity, although limited by availability and operative risk. The gut hormones Glucagon-like peptide-1 (GLP-1), Peptide YY (PYY), and Oxyntomodulin (OXM) are elevated postprandially after RYGB, which has been postulated to contribute to its metabolic benefits.Objective:We hypothesized that infusion of the three gut hormones to achieve levels similar to those encountered postprandially in RYGB patients might be effective in suppressing appetite. The aim of this study was to investigate the effect of a continuous infusion of GLP-1, OXM, and PYY (GOP) on energy intake and expenditure in obese volunteers.Methods:Obese volunteers were randomized to receive an infusion of GOP or placebo in a single-blinded, randomized, placebo-controlled crossover study for 10.5 hours a day. This was delivered subcutaneously using a pump device, allowing volunteers to remain ambulatory. Ad libitum food intake studies were performed during the infusion, and energy expenditure was measured using a ventilated hood calorimeter.Results:Postprandial levels of GLP-1, OXM, and PYY seen post RYGB were successfully matched using 4 pmol/kg/min, 4 pmol/kg/min, and 0.4 pmol/kg/min, respectively. This dose led to a mean reduction of 32% in food intake. No significant effects on resting energy expenditure were observed.Conclusion:This is, to our knowledge, the first time that an acute continuous subcutaneous infusion of GOP, replicating the postprandial levels observed after RYGB, is shown to be safe and effective in reducing food intake. This data suggests that triple hormone therapy might be a useful tool against obesity.
Highlights
Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment of obesity, limited by availability and operative risk
No significant effects on resting energy expenditure were observed. This is, to our knowledge, the first time that an acute continuous subcutaneous infusion of GOP, replicating the postprandial levels observed after RYGB, is shown to be safe and effective in reducing food intake
Following an initial dose-finding study, in which individual peptides were given for periods of up to 10 hours to volunteers to determine the steady-state plasma levels, we found that a combination of Glucagon-like peptide-1 (GLP-1) at 4 pmol/kg/min, OXM at 4 pmol/ kg/min, and Peptide YY (PYY) at 0.4 pmol/kg/min was able to replicate the postprandial levels seen after RYGB
Summary
Obese volunteers were randomized to receive an infusion of GOP or placebo in a singleblinded, randomized, placebo-controlled crossover study for 10.5 hours a day. This was delivered subcutaneously using a pump device, allowing volunteers to remain ambulatory. Day 1 consisted of a positive acclimatization visit whereby all volunteers received a lower dose GOP infusion (see below) to limit the effects of stress caused by subjects being unfamiliar with study procedures. A cannula attached to the infusion pump was positioned in the abdominal subcutis allowing for a 10.5-hour infusion. On day 2, volunteers were randomized in a single-blinded fashion to receive either GOP or 0.9% saline for 10.5 hours following the same protocol as on day 1. On day 3, the volunteers were given either GOP or 0.9% saline infusion, whichever had not been given on day 2
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
