Abstract
ContextThe gut-derived peptide hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are regulators of energy intake and glucose homeostasis and are thought to contribute to the glucose-lowering effects of bariatric surgery.ObjectiveTo establish the metabolomic effects of a combined infusion of GLP-1, OXM, and PYY (tripeptide GOP) in comparison to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD).Design and SettingSubanalysis of a single-blind, randomized, placebo-controlled study of GOP infusion (ClinicalTrials.gov NCT01945840), including VLCD and RYGB comparator groups.Patients and InterventionsTwenty-five obese patients with type 2 diabetes or prediabetes were randomly allocated to receive a 4-week subcutaneous infusion of GOP (n = 14) or 0.9% saline control (n = 11). An additional 22 patients followed a VLCD, and 21 underwent RYGB surgery.Main Outcome MeasuresPlasma and urine samples collected at baseline and 4 weeks into each intervention were subjected to cross-platform metabolomic analysis, followed by unsupervised and supervised modeling approaches to identify similarities and differences between the effects of each intervention.ResultsAside from glucose, very few metabolites were affected by GOP, contrasting with major metabolomic changes seen with VLCD and RYGB.ConclusionsTreatment with GOP provides a powerful glucose-lowering effect but does not replicate the broader metabolomic changes seen with VLCD and RYGB. The contribution of these metabolomic changes to the clinical benefits of RYGB remains to be elucidated.
Highlights
We previously reported that tripeptide GOP infusion led to better glucose tolerance in response to a mixed meal test but less weight loss than very low-calorie diet (VLCD) and Roux-en-Y gastric bypass (RYGB) [6]
We first performed untargeted metabolomic analysis on pre- and postintervention plasma and urine samples to identify patterns of change in an unbiased manner, without focusing on specific metabolites. It is immediately apparent from visual inspection of the metabolomic changes between pre- and postintervention timepoints (Fig. 2A) that the impact of GOP was less marked than of RYGB and VLCD and, in many cases, similar to that seen with SAL
This was further investigated using linear mixed effects (LME) modeling to formally determine the proportion of changes that were significantly different between interventions (Fig. 2B). This indicated that, when compared to SAL, up to one third of the observed plasma LC-MS features were distinctly altered by RYGB or VLCD, whereas no features were significantly altered by GOP after false discovery rate (FDR) correction
Summary
To establish the metabolomic effects of a combined infusion of GLP-1, OXM, and PYY in comparison to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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
