Antagonistic interaction between central glucagon-like Peptide-1 and oxytocin on diet-induced obesity mice

Jeonghoon Lee; Haneul Moon; Hyunji Lee; Yunkyeong Oh; Changyeon Kim; Young Hee Lee; Min Sun Kim; Cherl NamKoong; Hee Won Lee; Jung Hee Kim; Hyung Jin Choi

doi:10.1016/j.heliyon.2020.e05190

Antagonistic interaction between central glucagon-like Peptide-1 and oxytocin on diet-induced obesity mice

Heliyon. 2020 Oct 11;6(10):e05190. doi: 10.1016/j.heliyon.2020.e05190. eCollection 2020 Oct.

Authors

Affiliations

¹ Functional Neuroanatomy of Metabolism Regulation Laboratory, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.
² Functional Neuroanatomy of Metabolism Regulation Laboratory, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
³ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Abstract

Glucagon-like peptide-1 (GLP-1), whose agonists are widely prescribed, is a peptide proven effective in reducing obesity. Similarly, oxytocin (OXT) is a peptide known to increase satiety and help reduce body weight. In the present study, we aimed to examine the metabolic effects of co-administration of GLP-1 and OXT in diet-induced obesity (DIO) mice to elucidate their functions and interactions in the central nervous system. To this end, 40 DIO mice were subjected to stereotaxic surgery for the installation of an osmotic minipump and intracerebroventricular administration of GLP-1, OXT, or both. Initially, it was anticipated that co-administration of these anorexigenic peptides would be as effective as, if not more than, either GLP-1 or OXT alone in providing metabolic benefits to the obese mice. Interestingly, co-administration of OXT and GLP-1 offset the reductions in body weight and food intake promoted by either peptide alone. Co-administration also negated the decrease in fat and increase in lean mass produced by either peptide alone. Moreover, co-administration showed an equivalent calorimetric benefit as either peptide alone. Therefore, these results suggest antagonistic, rather than synergistic or additive, effects of centrally administered GLP-1 and OXT that attenuate the metabolic benefits of either peptide.

Keywords: Antagonism; Calorimetry; Diet; Glucagon-like peptide-1 (GLP-1); Metabolism; Molecular neuroscience; Nervous system; Neuropeptides; Obesity; Oxytocin (OXT); Peptides.