AUTHOR=Dischinger Ulrich , Hasinger Julia , Königsrainer Malina , Corteville Carolin , Otto Christoph , Fassnacht Martin , Hankir Mohamed , Seyfried Florian Johannes David 

TITLE=Toward a Medical Gastric Bypass: Chronic Feeding Studies With Liraglutide + PYY3-36 Combination Therapy in Diet-Induced Obese Rats

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.598843

DOI=10.3389/fendo.2020.598843

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>Combination therapies of anorectic gut hormones partially mimic the beneficial effects of bariatric surgery. Thus far, the effects of a combined chronic systemic administration of Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY<sub>3-36</sub>) have not been directly compared to Roux-en-Y gastric bypass (RYGB) in a standardized experimental setting.</p></sec><sec><title>Methods</title><p>High-fat diet (HFD)-induced obese male Wistar rats were randomized into six treatment groups: (1) RYGB, (2) sham-operation (shams), (3) liraglutide, (4) PYY<sub>3-36</sub>, (5) PYY<sub>3-36</sub>+liraglutide (6), saline. Animals were kept on a free choice high- and low-fat diet. Food intake, preference, and body weight were measured daily for 4 weeks. Open field (OP) and elevated plus maze (EPM) tests were performed.</p></sec><sec><title>Results</title><p>RYGB reduced food intake and achieved sustained weight loss. Combined PYY<sub>3-36</sub>+liraglutide treatment led to similar and plateaued weight loss compared to RYGB. Combined PYY<sub>3-36</sub>+liraglutide treatment was superior to PYY<sub>3-36</sub> (p ≤ 0.0001) and liraglutide (p ≤ 0.05 or p ≤ 0.01) mono-therapy. PYY<sub>3-36</sub>+liraglutide treatment and RYGB also reduced overall food intake and (less pronounced) high-fat preference compared to controls. The animals showed no signs of abnormal behavior in OF or EPM.</p></sec><sec><title>Conclusions</title><p>Liraglutide and PYY<sub>3-36</sub> combination therapy vastly mimics reduced food intake, food choice and weight reducing benefits of RYGB.</p></sec>