{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:05:33Z","timestamp":1784948733349,"version":"3.55.0"},"reference-count":96,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":62,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 HL128970"],"award-info":[{"award-number":["R01 HL128970"]}]},{"name":"NIH","award":["R01 HL133100"],"award-info":[{"award-number":["R01 HL133100"]}]},{"name":"AHA","award":["#915167"],"award-info":[{"award-number":["#915167"]}]},{"name":"AHA","award":["24CDA1270910"],"award-info":[{"award-number":["24CDA1270910"]}]},{"name":"NIH","award":["R01 HL128970"],"award-info":[{"award-number":["R01 HL128970"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,16]]},"abstract":"<jats:p>\n                    Weight loss medications are emerging candidates for pharmacotherapy of sleep-disordered breathing (SDB). A melanocortin 4 receptor (MC4R) agonist, setmelanotide (Set), is used to treat obesity caused by abnormal melanocortin and leptin signaling. We hypothesized that Set can treat SDB in mice with diet-induced obesity. We performed a proof-of-concept randomized crossover trial of a single dose of Set versus vehicle and a 2-week daily Set versus vehicle trial, examined colocalization of\n                    <jats:italic>Mc4r<\/jats:italic>\n                    mRNAs with the markers of CO\n                    <jats:sub>2<\/jats:sub>\n                    -sensing neurons\n                    <jats:italic>Phox2b<\/jats:italic>\n                    and neuromedin B in the brainstem, and expressed\n                    <jats:italic>Cre<\/jats:italic>\n                    -dependent designer receptors exclusively activated by designer drugs (DREADDs) or caspase in obese\n                    <jats:italic>Mc4r-Cre<\/jats:italic>\n                    mice. Set increased minute ventilation across sleep\/wake states, enhanced the hypercapnic ventilatory response (HCVR), and abolished apneas during sleep.\n                    <jats:italic>Phox2b<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    neurons in the nucleus of the solitary tract (NTS) and the parafacial region expressed\n                    <jats:italic>Mc4r<\/jats:italic>\n                    . Chemogenetic stimulation of the MC4R\n                    <jats:sup>+<\/jats:sup>\n                    neurons in the parafacial region, but not in the NTS, augmented HCVR without any changes in metabolism. Caspase elimination of the parafacial MC4R\n                    <jats:sup>+<\/jats:sup>\n                    neurons abolished effects of Set on HCVR. Parafacial MC4R\n                    <jats:sup>+<\/jats:sup>\n                    neurons projected to the respiratory premotor neurons retrogradely labeled from C3\u2013C4. In conclusion, MC4R agonists enhance the HCVR and treat SDB by acting on the parafacial MC4R\n                    <jats:sup>+<\/jats:sup>\n                    neurons.\n                  <\/jats:p>","DOI":"10.1172\/jci177823","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T12:00:38Z","timestamp":1744718438000},"source":"Crossref","is-referenced-by-count":9,"title":["Targeting melanocortin 4 receptor to treat sleep-disordered breathing in mice"],"prefix":"10.1172","volume":"135","author":[{"given":"Mateus R.","family":"Amorim","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC, USA."},{"name":"Department of Physiology, Medical School of Ribeir\u00e3o Preto, Sao Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah R.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Aung","sequence":"additional","affiliation":[{"name":"Medical College of Wisconsin, Milwaukee, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie Alexis","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Anokye-Danso","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junia L.","family":"de Deus","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC, 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