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Exaggerated hypoxic chemoreflex is a cardinal trait of SDB in obesity. We have shown that leptin acts in the carotid bodies (CB) to augment chemoreflex and that leptin activates the transient receptor potential melastatin 7 (TRPM7) channel. However, the effect of leptin\u2010TRPM7\u00a0signalling in CB on breathing and SDB has not been characterized in diet\u2010induced obesity (DIO). We hypothesized that leptin acts via TRPM7 in the CB to increase chemoreflex leading to SDB in obesity. DIO mice were implanted with EEG\/EMG electrodes and transfected with <jats:italic>Lepr<jats:sup>b<\/jats:sup><\/jats:italic> short hairpin RNA (shRNA) or <jats:italic>Trpm7<\/jats:italic> shRNA <jats:italic>vs<\/jats:italic>. control shRNA in the CB area bilaterally. Mice underwent a full\u2010polysomnography and metabolic studies at baseline and after transfection. Ventilatory responses to hypoxia and hypercapnia were assessed during wakefulness. <jats:italic>Lepr<jats:sup>b<\/jats:sup><\/jats:italic> and <jats:italic>Trpm7<\/jats:italic> were upregulated and their promoters were demethylated in the CB of DIO mice. <jats:italic>Lepr<jats:sup>b<\/jats:sup><\/jats:italic> knockdown in the CB did not significantly affect ventilation. <jats:italic>Trpm<\/jats:italic>7 knockdown in the CB stimulated breathing during sleep in normoxia. These effects were not driven by changes in CB chemosensitivity or metabolism. Under sustained hypoxia, <jats:italic>Trpm7<\/jats:italic> shRNA in the CB augmented ventilation during sleep, but decreased oxyhaemoglobin saturation. We conclude that the suppression of TRPM7 in the CB improved sleep\u2010related hypoventilation and that the respiratory effects of CB TRPM7 channels in obesity are independent of leptin. TRPM7\u00a0signalling in the CB could be a therapeutic target for the treatment of obesity\u2010related SDB.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15310-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The leptin\u2010TRPM7 axis in the carotid bodies may play an important role in the pathogenesis of sleep\u2010disordered breathing.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>TRPM7 channels regulate breathing during sleep by acting peripherally in the carotid bodies.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Suppression of TRPM7\u00a0signalling in the carotid bodies improves the obesity\u2010induced hypoventilation in mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pharmacological blockade of TRPM7 channels in the carotid bodies could be a therapy for sleep\u2010disordered breathing in obesity.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp283678","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T14:30:39Z","timestamp":1665412239000},"page":"5145-5162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["TRPM7 channels regulate breathing during sleep in obesity by acting peripherally in the carotid bodies"],"prefix":"10.1113","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6828-5132","authenticated-orcid":false,"given":"Lenise J.","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi\u2010Kyung","family":"Shin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huy","family":"Pho","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Yee","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishitha","family":"Hosamane","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3992-9234","authenticated-orcid":false,"given":"Frederick","family":"Anokye\u2010Danso","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Diabetes, and Metabolism Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rexford S.","family":"Ahima","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Diabetes, and Metabolism Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3571-8712","authenticated-orcid":false,"given":"James S. 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