Yasmina Dumiaty, Brett M. Underwood, Jenny Phy-Lim, Melissa J. Chee
{"title":"胰高血糖素样肽 1 和肽 YY3-36 在抑制食物、觅药和焦虑生成中的作用所依赖的神经回路","authors":"Yasmina Dumiaty, Brett M. Underwood, Jenny Phy-Lim, Melissa J. Chee","doi":"10.1016/j.npep.2024.102427","DOIUrl":null,"url":null,"abstract":"<div><p>Obesity is a critical health condition worldwide that increases the risks of comorbid chronic diseases, but it can be managed with weight loss. However, conventional interventions relying on diet and exercise are inadequate for achieving and maintaining weight loss, thus there is significant market interest for pharmaceutical anti-obesity agents. For decades, receptor agonists for the gut peptide glucagon-like peptide 1 (GLP-1) featured prominently in anti-obesity medications by suppressing appetite and food reward to elicit rapid weight loss. As the neurocircuitry underlying food motivation overlaps with that for drugs of abuse, GLP-1 receptor agonism has also been shown to decrease substance use and relapse, thus its therapeutic potential may extend beyond weight management to treat addictions. However, as prolonged use of anti-obesity drugs may increase the risk of mood-related disorders like anxiety and depression, and individuals taking GLP-1-based medication commonly report feeling demotivated, the long-term safety of such drugs is an ongoing concern. Interestingly, current research now focuses on dual agonist approaches that include GLP-1 receptor agonism to enable synergistic effects on weight loss or associated functions. GLP-1 is secreted from the same intestinal cells as the anorectic gut peptide, Peptide YY<sub>3</sub><sub>–</sub><sub>36</sub> (PYY<sub>3</sub><sub>–</sub><sub>36</sub>), thus this review assessed the therapeutic potential and underlying neural circuits targeted by PYY<sub>3</sub><sub>–</sub><sub>36</sub> when administered independently or in combination with GLP-1 to curb the appetite for food or drugs of abuse like opiates, alcohol, and nicotine. Additionally, we also reviewed animal and human studies to assess the impact, if any, for GLP-1 and/or PYY<sub>3</sub><sub>–</sub><sub>36</sub> on mood-related behaviors in relation to anxiety and depression. As dual agonists targeting GLP-1 and PYY<sub>3</sub><sub>–</sub><sub>36</sub> may produce synergistic effects, they can be effective at lower doses and offer an alternative approach for therapeutic benefits while mitigating undesirable side effects.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"105 ","pages":"Article 102427"},"PeriodicalIF":2.5000,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S014341792400026X/pdfft?md5=e5b0a1bb8019f231bc08035df63b0fa1&pid=1-s2.0-S014341792400026X-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Neurocircuitry underlying the actions of glucagon-like peptide 1 and peptide YY3–36 in the suppression of food, drug-seeking, and anxiogenesis\",\"authors\":\"Yasmina Dumiaty, Brett M. Underwood, Jenny Phy-Lim, Melissa J. Chee\",\"doi\":\"10.1016/j.npep.2024.102427\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Obesity is a critical health condition worldwide that increases the risks of comorbid chronic diseases, but it can be managed with weight loss. However, conventional interventions relying on diet and exercise are inadequate for achieving and maintaining weight loss, thus there is significant market interest for pharmaceutical anti-obesity agents. For decades, receptor agonists for the gut peptide glucagon-like peptide 1 (GLP-1) featured prominently in anti-obesity medications by suppressing appetite and food reward to elicit rapid weight loss. As the neurocircuitry underlying food motivation overlaps with that for drugs of abuse, GLP-1 receptor agonism has also been shown to decrease substance use and relapse, thus its therapeutic potential may extend beyond weight management to treat addictions. However, as prolonged use of anti-obesity drugs may increase the risk of mood-related disorders like anxiety and depression, and individuals taking GLP-1-based medication commonly report feeling demotivated, the long-term safety of such drugs is an ongoing concern. Interestingly, current research now focuses on dual agonist approaches that include GLP-1 receptor agonism to enable synergistic effects on weight loss or associated functions. GLP-1 is secreted from the same intestinal cells as the anorectic gut peptide, Peptide YY<sub>3</sub><sub>–</sub><sub>36</sub> (PYY<sub>3</sub><sub>–</sub><sub>36</sub>), thus this review assessed the therapeutic potential and underlying neural circuits targeted by PYY<sub>3</sub><sub>–</sub><sub>36</sub> when administered independently or in combination with GLP-1 to curb the appetite for food or drugs of abuse like opiates, alcohol, and nicotine. Additionally, we also reviewed animal and human studies to assess the impact, if any, for GLP-1 and/or PYY<sub>3</sub><sub>–</sub><sub>36</sub> on mood-related behaviors in relation to anxiety and depression. As dual agonists targeting GLP-1 and PYY<sub>3</sub><sub>–</sub><sub>36</sub> may produce synergistic effects, they can be effective at lower doses and offer an alternative approach for therapeutic benefits while mitigating undesirable side effects.</p></div>\",\"PeriodicalId\":19254,\"journal\":{\"name\":\"Neuropeptides\",\"volume\":\"105 \",\"pages\":\"Article 102427\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-03-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S014341792400026X/pdfft?md5=e5b0a1bb8019f231bc08035df63b0fa1&pid=1-s2.0-S014341792400026X-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuropeptides\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S014341792400026X\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropeptides","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S014341792400026X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Neurocircuitry underlying the actions of glucagon-like peptide 1 and peptide YY3–36 in the suppression of food, drug-seeking, and anxiogenesis
Obesity is a critical health condition worldwide that increases the risks of comorbid chronic diseases, but it can be managed with weight loss. However, conventional interventions relying on diet and exercise are inadequate for achieving and maintaining weight loss, thus there is significant market interest for pharmaceutical anti-obesity agents. For decades, receptor agonists for the gut peptide glucagon-like peptide 1 (GLP-1) featured prominently in anti-obesity medications by suppressing appetite and food reward to elicit rapid weight loss. As the neurocircuitry underlying food motivation overlaps with that for drugs of abuse, GLP-1 receptor agonism has also been shown to decrease substance use and relapse, thus its therapeutic potential may extend beyond weight management to treat addictions. However, as prolonged use of anti-obesity drugs may increase the risk of mood-related disorders like anxiety and depression, and individuals taking GLP-1-based medication commonly report feeling demotivated, the long-term safety of such drugs is an ongoing concern. Interestingly, current research now focuses on dual agonist approaches that include GLP-1 receptor agonism to enable synergistic effects on weight loss or associated functions. GLP-1 is secreted from the same intestinal cells as the anorectic gut peptide, Peptide YY3–36 (PYY3–36), thus this review assessed the therapeutic potential and underlying neural circuits targeted by PYY3–36 when administered independently or in combination with GLP-1 to curb the appetite for food or drugs of abuse like opiates, alcohol, and nicotine. Additionally, we also reviewed animal and human studies to assess the impact, if any, for GLP-1 and/or PYY3–36 on mood-related behaviors in relation to anxiety and depression. As dual agonists targeting GLP-1 and PYY3–36 may produce synergistic effects, they can be effective at lower doses and offer an alternative approach for therapeutic benefits while mitigating undesirable side effects.
期刊介绍:
The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems.
The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.