Associations of <scp>PYY</scp> , <scp>GLP</scp> ‐1 and <scp>LEAP2</scp> with changes in feeding‐related cognition, body weight and glucose homeostasis after bariatric surgery in non‐diabetic women

Roux-en-Y gastric bypass (RYGB) is an effective surgical intervention for severe obesity, but the role of gastrointestinal hormones in its benefits remains unclear. We examined longitudinal pre-to-post-meal gastrointestinal hormone changes and their relationships with glucose homeostasis and feeding-related cognitive responses in women undergoing RYGB. Seventeen non-diabetic women were evaluated pre-RYGB (Visit 1, V1), 1-month post-RYGB (Visit 2, V2), and 1-year post-RYGB (Visit 3, V3). Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), ghrelin, and liver-expressed antimicrobial peptide 2 (LEAP2) were measured before and after a breakfast in all visits. Appetite ratings and feeding-related cognitive performance were evaluated using visual analog scales, Ideal Portion Size, and Food Stroop tasks. At V3, RYGB induced weight loss (30.8%) and improved glucose homeostasis (p = .020), accompanied by reduced hunger (p = .042), smaller self-reported ideal portion size (p < .001), and improved cognitive control toward food-cues (p = .002). Fasting GLP-1 and PYY levels remained stable across visits but showed enhanced post-meal responses at V2 and V3 (GLP-1: p < .001; PYY: p = .013). Ghrelin levels increased post-RYGB (p = .010) without post-meal variation. LEAP2 concentrations remained stable. Fasting LEAP2 correlated positively with BMI at V1 (p < .001). Fasting PYY correlated inversely with BMI at V3 (p = .005), and its post-meal rise inversely correlated with ideal portion size at V1 (p = .022). GLP-1 increments negatively correlated with ideal portion size (p = .007) at all visits and glycemia (p = .017) at V1. In non-diabetic women, RYGB improves feeding-related cognitive processes. BMI is associated with LEAP2 only pre-surgery, and with PYY 1-year post-RYGB. Restoration of GLP-1 and PYY post-meal increments contributes to metabolic and behavioral improvements. Clinical Trial Registry: This study was registered at clinicaltrials.gov as NCT01815216. https://clinicaltrials.gov/study/NCT01815216.