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However, the effect of leptin on minute ventilation (\n V<\/jats:italic>\n E<\/jats:sub>\n ) and the hypoxic ventilatory response (HVR) has not been sufficiently studied.\n <\/jats:p>\n <\/jats:list-item>\n \n \n We report that\n \n LepR\n b<\/jats:sup>\n <\/jats:italic>\n is present in approximately 74% of the CB glomus cells.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Leptin increased carotid sinus nerve activity at baseline and in response to hypoxia\n in\u00a0vivo<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:list-item>\n \n \n Subcutaneous infusion of leptin increased\n V<\/jats:italic>\n E<\/jats:sub>\n and HVR in C57BL\/6J mice and this effect was abolished by CB denervation.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Expression of\n \n LepR\n b<\/jats:sup>\n <\/jats:italic>\n in the carotid bodies of\n \n LepR\n b<\/jats:sup>\n <\/jats:italic>\n deficient obese\n db\/db<\/jats:italic>\n mice increased V\n E<\/jats:sub>\n during wakefulness and sleep and augmented the HVR.\n <\/jats:p>\n <\/jats:list-item>\n \n \n We conclude that leptin acts on\n \n LepR\n b<\/jats:sup>\n <\/jats:italic>\n in the CBs to stimulate breathing and HVR, which may protect against sleep disordered breathing in obesity.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Abstract<\/jats:title>\n \n Leptin is a potent respiratory stimulant. The carotid bodies (CB) express the long functional isoform of leptin receptor,\n \n LepR\n b<\/jats:sup>\n <\/jats:italic>\n , but the role of leptin in CB has not been fully elucidated. The objectives of the current study were (1) to examine the effect of subcutaneous leptin infusion on minute ventilation (\n V<\/jats:italic>\n E<\/jats:sub>\n ) and the hypoxic ventilatory response to 10% O\n 2<\/jats:sub>\n (HVR) in C57BL\/6J mice before and after CB denervation; (2) to express\n \n LepR\n b<\/jats:sup>\n <\/jats:italic>\n in CB of\n \n LepR\n b<\/jats:sup>\n <\/jats:italic>\n \u2010deficient obese\n db<\/jats:italic>\n \/\n db<\/jats:italic>\n mice and examine its effects on breathing during sleep and wakefulness and on HVR. We found that leptin enhanced carotid sinus nerve activity at baseline and in response to 10% O\n 2<\/jats:sub>\n in\u00a0vivo<\/jats:italic>\n . In C57BL\/6J mice, leptin increased\n V<\/jats:italic>\n E<\/jats:sub>\n from 1.1 to 1.5\u00a0mL\/min\/g during normoxia (\n P<\/jats:italic>\n \u00a0< 0.01) and from 3.6 to 4.7\u00a0mL\/min\/g during hypoxia (\n P<\/jats:italic>\n \u00a0< 0.001), augmenting HVR from 0.23 to 0.31\u00a0mL\/min\/g\/\u0394\n \n (\n P<\/jats:italic>\n \u00a0< 0.001). The effects of leptin on\n V<\/jats:italic>\n E<\/jats:sub>\n and HVR were abolished by CB denervation. In\n db<\/jats:italic>\n \/\n db<\/jats:italic>\n mice,\n LepR<\/jats:italic>\n b<\/jats:sup>\n expression in CB increased\n V<\/jats:italic>\n E<\/jats:sub>\n from 1.1 to 1.3\u00a0mL\/min\/g during normoxia (\n P<\/jats:italic>\n \u00a0< 0.05) and from 2.8 to 3.2\u00a0mL\/min\/g during hypoxia (\n P<\/jats:italic>\n \u00a0< 0.02), increasing HVR. Compared to control\n db<\/jats:italic>\n \/\n db<\/jats:italic>\n mice,\n \n LepR\n b<\/jats:sup>\n <\/jats:italic>\n transfected mice showed significantly higher\n V<\/jats:italic>\n E<\/jats:sub>\n throughout non\u2010rapid eye movement (20.1\n vs<\/jats:italic>\n . \u221227.7\u00a0mL\/min respectively,\n P<\/jats:italic>\n \u00a0< 0.05) and rapid eye movement sleep (16.5\u00a0\n vs<\/jats:italic>\n 23.4\u00a0mL\/min,\n P<\/jats:italic>\n \u00a0< 0.05). We conclude that leptin acts in CB to augment\n V<\/jats:italic>\n E<\/jats:sub>\n and HVR, which may protect against sleep disordered breathing in obesity.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp276900","type":"journal-article","created":{"date-parts":[[2018,10,5]],"date-time":"2018-10-05T17:47:15Z","timestamp":1538761635000},"page":"151-172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Leptin acts in the carotid bodies to increase minute ventilation during wakefulness and sleep and augment the hypoxic ventilatory response"],"prefix":"10.1113","volume":"597","author":[{"given":"Candela","family":"Caballero\u2010Eraso","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USA"},{"name":"Unidad M\u00e9dico\u2010Quir\u00fargica de Enfermedades Respiratorias Instituto de Biomedicina de Sevilla (IBiS) Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES) Hospital Universitario Virgen del Roc\u00edo\/Universidad de Sevilla Sevilla Spain"}],"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":"Lenise J","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USA"},{"name":"Departamento de Psicobiologia Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis E.","family":"Pichard","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\/0000-0001-9690-1257","authenticated-orcid":false,"given":"Zhi\u2010Juan","family":"Wu","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":"Chenjuan","family":"Gu","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":"Slava","family":"Berger","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":"Luu","family":"Pham","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":"Ho\u2010Yee (Bonnie)","family":"Yeung","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Engineering Johns Hopkins Bloomberg School of Public Health Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machiko","family":"Shirahata","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Engineering Johns Hopkins Bloomberg School of Public Health Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Schwartz","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 (Winnie)","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Engineering Johns Hopkins Bloomberg School of Public Health Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S. 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