ArticleActa physiologica (Oxford, England)2015
Activation of the brain melanocortin system is required for leptin-induced modulation of chemorespiratory function.
Article in Acta physiologica (Oxford, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Cardiometabolic regulation by adipocyte-derived leptin and the brain melanocortin system.Clinical science (London, England : 1979) · 2026Review
- Metastatic promoting role of mesenchymal stem cells in oral squamous cell carcinoma revealed by an improved bone marrow chimeric model.Scientific reports · 2026Article
- Leptin antagonism improves Rett syndrome phenotype in symptomatic Mecp2-deficient mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Melanocortin receptor 4 agonist setmelanotide treats opioid-induced respiratory depression.bioRxiv : the preprint server for biology · 2026Article
- Review
- Article
- A Leptin-Mediated Neural Mechanism Linking Breathing to Metabolism.Cell reports · 2020Article
- CNS Regulation of Glucose Homeostasis: Role of the Leptin-Melanocortin System.Current diabetes reports · 2020Review
- The α2,3-selective potentiator of GABAPharmacology, biochemistry, and behavior · 2019Article
- Role of melanocortin 4 receptor in hypertension induced by chronic intermittent hypoxia.Acta physiologica (Oxford, England) · 2019Article
- Intranasal Leptin Relieves Sleep-disordered Breathing in Mice with Diet-induced Obesity.American journal of respiratory and critical care medicine · 2019Article
- High-fat diet increases respiratory frequency and abdominal expiratory motor activity during hypercapnia.Respiratory physiology & neurobiology · 2018Article
- Uncoupling protein 3 deficiency impairs myocardial fatty acid oxidation and contractile recovery following ischemia/reperfusion.Basic research in cardiology · 2018Article
- Article
- Effects of nalfurafine on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone: modeling an abuse-deterrent opioid analgesic in rats.Psychopharmacology · 2017Article
- Regulation of Blood Pressure, Appetite, and Glucose by CNS Melanocortin System in Hyperandrogenemic Female SHR.American journal of hypertension · 2016Article
- Article
- Facilitation of breathing by leptin effects in the central nervous system.The Journal of physiology · 2016Review
- Neuroendocrinological and Epigenetic Mechanisms Subserving Autonomic Imbalance and HPA Dysfunction in the Metabolic Syndrome.Frontiers in neuroscience · 2016Review
- Developmental Origins of Cardiometabolic Diseases: Role of the Maternal Diet.Frontiers in physiology · 2016Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledMelanocortin receptors (MC3/4R) mediate most of the metabolic and cardiovascular actions of leptin.
aimHere, we tested if MC4R also contributes to leptin's effects on respiratory function.
methodsAfter control measurements, male Holtzman rats received daily microinjections of leptin, SHU9119 (MC3/4R antagonist) or SHU9119 combined with leptin infused into the brain lateral ventricle for 7 days. On the 6th day of treatment, tidal volume (VT ), respiratory frequency (fR ) and pulmonary ventilation (VE ) were measured by whole-body plethysmography during normocapnia or hypercapnia (7% CO2 ). Baseline mean arterial pressure (MAP), heart rate (HR) and metabolic rate were also measured. VE , VT and fR were also measured in mice with leptin receptor deletion in the entire central nervous system (LepR/Nestin-cre) or only in proopiomelanocortin neurones (LepR/POMC-cre) and in MC4R knockout (MC4R(-/-) ) and wild-type mice.
resultsLeptin (5 μg day(-1) ) reduced body weight (~17%) and increased ventilatory response to hypercapnia, whereas SHU9119 (0.6 nmol day(-1) ) increased body weight (~18%) and reduced ventilatory responses compared with control-PBS group (Lep: 2119 ± 90 mL min(-1) kg(-1) and SHU9119: 997 ± 67 mL min(-1) kg(-1) , vs. PBS: 1379 ± 91 mL min(-1) kg(-1) ). MAP increased after leptin treatment (130 ± 2 mmHg) compared to PBS (106 ± 3 mmHg) or SHU9119 alone (109 ± 3 mmHg). SHU9119 prevented the effects of leptin on body weight, MAP (102 ± 3 mmHg) and ventilatory response to hypercapnia (1391 ± 137 mL min(-1) kg(-1) ). The ventilatory response to hypercapnia was attenuated in the LepR/Nestin-cre, LepR/POMC-cre and MC4R(-/-) mice.
conclusionThese results suggest that central MC4R mediate the effects of leptin on respiratory response to hypercapnia.
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