Yuko Maejima, Shoko Yokota, S. Hidema, Katsuhiko Nishimori, Heidi de Wet, Kenju Shimomura
{"title":"Systemic co-administration of low dose oxytocin and glucagon like peptide-1 additively decreases food intake and body weight.","authors":"Yuko Maejima, Shoko Yokota, S. Hidema, Katsuhiko Nishimori, Heidi de Wet, Kenju Shimomura","doi":"10.1159/000538792","DOIUrl":null,"url":null,"abstract":"INTRODUCTION\nGLP-1 receptor agonists are the number one drug prescribed for the treatment of obesity and type 2 diabetes. These drugs are not, however, without side-effects and in an effort to maximize therapeutic effect while minimizing adverse effects, gut hormone co-agonists received considerable attention as new drug targets in the fight against obesity. Numerous previous reports identified the neuropeptide oxytocin (OXT) as a promising anti-obesity drug. The aim of this study is to evaluate OXT as a possible co-agonist for GLP-1 and examine the effects of its co-administration on food intake (FI) and body weight (BW) in mice.\n\n\nMETHODS\nFI and c-Fos levels were measured in the feeding-centers of the brain in response to an intraperitoneal injection of saline, OXT, GLP-1 or OXT/GLP-1. The action potential frequency and cytosolic Ca2+ ([Ca2+]i) in response to OXT, GLP-1 or OXT/GLP-1were measured in ex-vivo PVN neuronal cultures. Finally, FI and BW changes were compared in diet induced obese mice treated with saline, OXT, GLP-1 or OXT/GLP-1 for 13 days.\n\n\nRESULTS\nSingle injection of OXT/GLP-1 additively decreased FI, and increased c-Fos expression specifically in the paraventricular (PVN) and supraoptic nucleus (SON). 70% of GLP-1 receptor positive neurons in the PVN also expressed OXT receptors, and OXT/GLP-1 co-administration dramatically increased firing and [Ca2+]i in the PVN OXT neurons. The chronic OXT/GLP-1 co-administration decreased BW without changing FI.\n\n\nCONCLUSION\nChronic OXT/GLP-1 co-administration decreases BW, possibly via the activation of PVN OXT neurons. OXT might be a promising candidate as an incretin co-agonist in obesity treatment.","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroendocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000538792","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
INTRODUCTION
GLP-1 receptor agonists are the number one drug prescribed for the treatment of obesity and type 2 diabetes. These drugs are not, however, without side-effects and in an effort to maximize therapeutic effect while minimizing adverse effects, gut hormone co-agonists received considerable attention as new drug targets in the fight against obesity. Numerous previous reports identified the neuropeptide oxytocin (OXT) as a promising anti-obesity drug. The aim of this study is to evaluate OXT as a possible co-agonist for GLP-1 and examine the effects of its co-administration on food intake (FI) and body weight (BW) in mice.
METHODS
FI and c-Fos levels were measured in the feeding-centers of the brain in response to an intraperitoneal injection of saline, OXT, GLP-1 or OXT/GLP-1. The action potential frequency and cytosolic Ca2+ ([Ca2+]i) in response to OXT, GLP-1 or OXT/GLP-1were measured in ex-vivo PVN neuronal cultures. Finally, FI and BW changes were compared in diet induced obese mice treated with saline, OXT, GLP-1 or OXT/GLP-1 for 13 days.
RESULTS
Single injection of OXT/GLP-1 additively decreased FI, and increased c-Fos expression specifically in the paraventricular (PVN) and supraoptic nucleus (SON). 70% of GLP-1 receptor positive neurons in the PVN also expressed OXT receptors, and OXT/GLP-1 co-administration dramatically increased firing and [Ca2+]i in the PVN OXT neurons. The chronic OXT/GLP-1 co-administration decreased BW without changing FI.
CONCLUSION
Chronic OXT/GLP-1 co-administration decreases BW, possibly via the activation of PVN OXT neurons. OXT might be a promising candidate as an incretin co-agonist in obesity treatment.
期刊介绍:
''Neuroendocrinology'' publishes papers reporting original research in basic and clinical neuroendocrinology. The journal explores the complex interactions between neuronal networks and endocrine glands (in some instances also immunecells) in both central and peripheral nervous systems. Original contributions cover all aspects of the field, from molecular and cellular neuroendocrinology, physiology, pharmacology, and the neuroanatomy of neuroendocrine systems to neuroendocrine correlates of behaviour, clinical neuroendocrinology and neuroendocrine cancers. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research, and special focus editions of topical interest.