GLP-1 and PYY for the treatment of obesity: a pilot study on the use of agonists and antagonists in diet-induced rats

被引：3

作者：

Oertel, Marie ^{[1
]}

Ziegler, Christian ^{[1
,3
]}

Kohlhaas, Michael ^{[2
]}

Nickel, Alexander ^{[2
]}

Kloock, Simon ^{[1
]}

Maack, Christoph ^{[2
]}

Sequeira, Vasco ^{[2
]}

Fassnacht, Martin ^{[1
]}

Dischinger, Ulrich ^{[1
,2
]}

机构：

[1] Univ Wurzburg, Univ Hosp, Dept Internal Med, Div Endocrinol & Diabet, Wurzburg, Germany

[2] Comprehens Heart Failure Ctr, Wurzburg, Germany

[3] Univ Hosp Carl Gustav Carus Dresden, Dept Internal Med 3, Dresden, Germany

来源：

ENDOCRINE CONNECTIONS | 2024年 / 13卷 / 03期

关键词：

obesity; semaglutide; glucagon-like peptide 1 (GLP-1); peptide tyrosine tyrosine 3-36 (PYY3-36); incretin analogs; REDUCES FOOD-INTAKE; PEPTIDE-YY; NEUROPEPTIDE-Y; BARIATRIC SURGERY; BODY-WEIGHT; GUT HORMONE; GLUCOSE-METABOLISM; RECEPTOR AGONIST; RODENT MODELS; ADIPOSITY;

D O I：

10.1530/EC-23-0398

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective Combination therapies with gut hormone analogs represent promising treatment strategies for obesity. This pilot study investigates the therapeutic potential of modulators of the glucagon-like peptide 1 (GLP-1) and neuropeptide Y (NPY) system using GLP-1 receptor agonists (semaglutide) and antagonists (exendin 9-39), as well as non-selective and NPY-Y2-receptor selective peptide tyrosine tyrosine (PYY) analogs (PYY3-36/NNC0165-0020 and NNC0165-1273) and an NPY-Y2 receptor antagonist (JNJ31020028).Methods High-fat diet (HFD)-induced obese rats were randomized into following treatment groups: group 1, nonselective PYY analog + semaglutide (n = 4); group 2, non-selective and NPY-Y2 receptor selective PYY analog + semaglutide (n = 2); group 3, GLP-1 receptor antagonist + NPY-Y2 receptor antagonist (n = 3); group 4, semaglutide (n = 5); and group 5, control (n = 5). Animals had free access to HFD and low-fat diet. Food intake, HFD preference and body weight were measured daily.Results A combinatory treatment with a non-selective PYY analog and semaglutide led to a maximum body weight loss of 14.0 +/- 4.9% vs 9.9 +/- 1.5% with semaglutide alone. Group 2 showed a maximum weight loss of 20.5 +/- 2.4%. While HFD preference was decreased in group 2, a strong increase in HFD preference was detected in group 3.Conclusions PYY analogs (especially NPY-Y2 selective receptor agonists) could represent a promising therapeutic approach for obesity in combination with GLP-1 receptor agonists. Additionally, combined GLP-1 and PYY3-36 receptor agonists might have beneficial effects on food preference.

引用

页数：12