Setmelanotide, a melanocortin-4-receptor agonist, increases the hypercapnic ventilatory response and relieves hypoventilation in obese mice

肥胖低通气综合征 医学 高碳酸血症 内分泌学 内科学 瘦素 通气不足 黑素皮质素 麻醉 肥胖 呼吸系统 受体
作者
O Aung,Mateus R. Amorim,Frederick Anokye‐Danso,Vsevolod Y. Polotsky
出处
期刊:Physiology [American Physiological Society]
卷期号:38 (S1) 被引量:1
标识
DOI:10.1152/physiol.2023.38.s1.5731024
摘要

Introduction: Obesity leads to high cardiorespiratory morbidity and mortality. Obese individuals can develop obesity hypoventilation syndrome (OHS) characterized by daytime hypercapnia in the absence of alternative underlying causes. OHS leads to daytime sleepiness, cardiovascular complications, and cyanosis. There is no effective pharmacotherapy for OHS. Leptin, an adipose-produced hormone, improves breathing in OHS, but obese individuals and rodents are resistant to the beneficial effects of leptin. The melanocortin axis is a downstream target of leptin but effects of this axis on control of breathing are poorly studied. Setmelanotide is an FDA-approved drug for weight loss that specifically binds to the melanocortin 4 receptor (MC4R). We have previously demonstrated that C57BL/6J mice with diet induced obesity (DIO) hypoventilate during sleep and exhibit all features of OHS. We hypothesized that the activation of MC4R by setmelanotide augments the control of breathing during sleep in DIO mice. Methods: We performed a proof-of-concept single dose randomized trial of intraperitoneal setmelanotide (1.0 mg/kg) vs vehicle in DIO C57BL/6J mice using a cross-over design. The injections were followed by sleep studies, and measurements of the hypercapnic ventilatory response, oxygen consumption (VO 2 ), and carbon dioxide production (VCO 2 ). Results: Activation of MC4R by setmelanotide increased inspiratory flow, respiratory rate, and minute ventilation during NREM and REM sleep compared to vehicle. Activation of MC4R by setmelanotide increased the hypercapnic ventilatory response. Setmelanotide also increased VCO 2 , and VO 2 , but the ventilation was increased out of proportion to the upregulation of metabolism, which was evident from increases in the VE/VO 2 and VE/VCO 2 ratios. Conclusion: Activation of MC4R by setmelanotide relieved hypoventilation during sleep and increased the hypercapnic ventilatory response in obese mice. Our study identified MC4 as a promising therapeutic target in OHS. NIH (R01 HL128970, R01 HL133100, and R01 HL138932), AHA (#915167). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
碧蓝的盼夏完成签到,获得积分10
4秒前
AU完成签到 ,获得积分10
5秒前
研友_yLpYkn完成签到,获得积分10
6秒前
兴奋的定帮完成签到 ,获得积分0
7秒前
一叶知秋应助大橙子采纳,获得10
8秒前
9秒前
金蛋蛋完成签到 ,获得积分10
9秒前
马琛尧完成签到 ,获得积分10
11秒前
一行白鹭上青天完成签到 ,获得积分10
15秒前
帅气的宽完成签到 ,获得积分10
16秒前
lixoii完成签到 ,获得积分10
18秒前
萌萌许完成签到,获得积分10
18秒前
sunce1990完成签到 ,获得积分10
21秒前
Bin_Liu完成签到,获得积分20
22秒前
宇老师完成签到,获得积分10
22秒前
研友_VZG7GZ应助马琛尧采纳,获得10
23秒前
安安的小板栗完成签到,获得积分10
26秒前
123_完成签到,获得积分10
28秒前
NexusExplorer应助大橙子采纳,获得10
29秒前
上善若水完成签到 ,获得积分10
31秒前
qiqi发布了新的文献求助10
35秒前
35秒前
英俊的铭应助cm采纳,获得10
36秒前
37秒前
量子星尘发布了新的文献求助10
37秒前
affy210310完成签到,获得积分10
38秒前
名字不好起完成签到,获得积分10
38秒前
齐朕完成签到,获得积分10
39秒前
大橙子发布了新的文献求助10
41秒前
speed完成签到 ,获得积分10
42秒前
RYK完成签到 ,获得积分10
43秒前
44秒前
cm发布了新的文献求助10
48秒前
50秒前
50秒前
50秒前
50秒前
50秒前
大力水手完成签到,获得积分0
52秒前
54秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038157
求助须知:如何正确求助?哪些是违规求助? 3575869
关于积分的说明 11373842
捐赠科研通 3305650
什么是DOI,文献DOI怎么找? 1819255
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022