Activation of the brain melanocortin system is required for leptin-induced modulation of chemorespiratory function

Author(s)

Bassi, M. ^[1] ; Nakamura, N. B. ^[1] ; Furuya, W. I. ^[1] ; Colombari, D. S. A. ^[1] ; Menani, J. V. ^[1] ; do Carmo, J. M. ^[2] ; da Silva, A. A. ^[2] ; Hall, J. E. ^[2] ; Colombari, E. ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Dept Physiol & Pathol, Sch Dent, BR-14801903 Araraquara - Brazil

^[2] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 - USA

• Document type: Journal article
• Source: ACTA PHYSIOLOGICA; v. 213, n. 4, p. 893-901, APR 2015.
• Web of Science Citations: 16

Abstract

Melanocortin receptors (MC3/4R) mediate most of the metabolic and cardiovascular actions of leptin. Aim: Here, we tested if MC4R also contributes to leptin's effects on respiratory function. Methods: After 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 (V-T), respiratory frequency (f(R)) and pulmonary ventilation (V-E) 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. V-E, V-T and f(R) 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. Results: Leptin (5 mu g day(-1)) reduced body weight (similar to 17%) and increased ventilatory response to hypercapnia, whereas SHU9119 (0.6 nmol day(-1)) increased body weight (similar to 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. Conclusion: These results suggest that central MC4R mediate the effects of leptin on respiratory response to hypercapnia. (AU)

• FAPESP's process: 09/54888-7 - Neural mechanisms involved on chemoreception
• Grantee: Eduardo Colombari
• Support Opportunities: Research Projects - Thematic Grants