{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:03:32Z","timestamp":1787807012627,"version":"build-2784847793"},"reference-count":55,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2025,8,10]],"date-time":"2025-08-10T00:00:00Z","timestamp":1754784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Diet\u2010induced obesity (DIO) is associated with increased circulating level of the hormone leptin. We have previously shown that leptin augments hypoxic ventilatory response in mice, and the response is abolished by carotid body (CB) denervation, and that leptin induces hypertension in DIO acting on transient receptor potential melastatin 7 (Trpm7) channels in CB. However CB chemosensory responses in DIO have not been sufficiently elucidated. The aim of this study was to examine the effects of DIO and leptin on carotid sinus nerve (CSN) activity and the role of Trpm7 at normoxic and hypoxic conditions. We measured afferent CSN activity using a novel <jats:italic>ex vivo<\/jats:italic> perfused CB preparation in four groups of mice on the C57BL\/6J background: lean wild type, DIO wildtype, Trpm7<jats:sup>flox<\/jats:sup>\u2010DIO transfected with adenoviral vectors harbouring <jats:italic>Cre<\/jats:italic>\u2010recombinase and green fluorescent protein (<jats:italic>Ad<\/jats:italic>\u2010<jats:italic>Cre<\/jats:italic>\u2010<jats:italic>GFP<\/jats:italic>) or control GFP (<jats:italic>Ad\u2010GFP<\/jats:italic>). Leptin augmented CSN responses to normoxic (PO<jats:sub>2<\/jats:sub>\u00a0=\u00a0100 Torr) and hypoxic (PO<jats:sub>2<\/jats:sub>\u00a0=\u00a060 Torr) conditions. Compared to lean male mice, in DIO mice (a) CSN response to hypoxia was 50% greater, (b) leptin had a greater impact on CSN activity at normoxic and hypoxic conditions. Leptin\u2010induced CSN activities were attenuated by Trpm7 antagonist FTY720 and by Trpm7 knockdown in CB. There was no significant difference between CB chemosensitivity response to leptin in male and female mice. We conclude that CB chemosensitivity is increased in DIO compared to lean mice, and CB Trpm7 channel could be a therapeutic target for obesity\u2010related hypertension.\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\/tjp70039-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>We have developed a novel <jats:italic>ex vivo<\/jats:italic> perfused murine carotid body (CB) preparation to evaluate carotid sinus nerve (CSN) activity using physiologically relevant levels of PO<jats:sub>2<\/jats:sub> at normoxic and hypoxic conditions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Diet\u2010induced obesity (DIO) increases baseline (normoxic) CSN activity, independent of leptin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>DIO augments CB hypoxic chemoreflex gain via leptin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The effect of leptin on CB hypoxic chemoreflex is completely abolished by a Trpm7 blocker FTY720 and prevented by Trpm7 knockdown in CB. FTY720 does not have any effect on CSN activity in the absence of leptin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Taken together our new findings provide direct evidence that obesity increases CB chemoreflex via the leptin\u2010Trpm7 pathway.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp288722","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:15:14Z","timestamp":1754871314000},"page":"4887-4905","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Diet\u2010induced obesity in mice increases carotid body chemosensitivity via the leptin\u2010TRPM7 pathway"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4383-4521","authenticated-orcid":false,"given":"Arijit","family":"Roy","sequence":"first","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medicine The George Washington 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