title: Leptin into the ventrolateral medulla facilitates chemorespiratory response in leptin-deficient (ob/ob) mice.
abstract: OBJECTIVE
  Leptin, an adipocyte-derived hormone, is suggested to participate in the central control of breathing. We hypothesized that leptin may facilitate ventilatory responses to chemoreflex activation by acting on respiratory nuclei of the ventrolateral medulla. The baseline ventilation and the ventilatory responses to CO2 were evaluated before and after daily injections of leptin into the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) for 3 days in obese leptin-deficient (ob/ob) mice.
  
  
  METHODS
  Male ob/ob mice (40-45 g, n = 7 per group) received daily microinjections of vehicle or leptin (1 μg per 100 nL) for 3 days into the RTN/pFRG. Respiratory responses to CO2 were measured by whole-body plethysmography.
  
  
  RESULTS
  Unilateral microinjection of leptin into the RTN/pFRG in ob/ob mice increased baseline ventilation (VE ) from 1447 ± 96 to 2405 ± 174 mL min(-1) kg(-1) by increasing tidal volume (VT ) from 6.4 ± 0.4 to 9.1 ± 0.8 mL kg(-1) (P < 0.05). Leptin also enhanced ventilatory responses to 7% CO2 (Δ = 2172 ± 218 mL min(-1) kg(-1) , vs. control: Δ = 1255 ± 105 mL min(-1) kg(-1) ), which was also due to increased VT (Δ = 4.71 ± 0.51 mL kg(-1) , vs. control: Δ = 2.27 ± 0.20 mL kg(-1) ), without changes in respiratory frequency. Leptin treatment into the RTN/pFRG or into the surrounding areas decreased food intake (83 and 70%, respectively), without significantly changing body weight.
  
  
  CONCLUSIONS
  The present results suggest that leptin acting in the respiratory nuclei of the ventrolateral medulla improves baseline VE and VT and facilitates respiratory responses to hypercapnia in ob/ob mice.
authors: Department of Physiology and Pathology, School of Dentistry, São Paulo State University (UNESP), Araraquara, SP, Brazil.
authors: M
authors: M
authors: Bassi
authors: W I
authors: WI
authors: Furuya
authors: J V
authors: JV
authors: Menani
authors: D S A
authors: DS
authors: Colombari
authors: J M
authors: JM
authors: do Carmo
authors: A A
authors: AA
authors: da Silva
authors: J E
authors: JE
authors: Hall
authors: T S
authors: TS
authors: Moreira
authors: I C
authors: IC
authors: Wenker
authors: D K
authors: DK
authors: Mulkey
authors: E
authors: E
authors: Colombari
mesh_terms: D000818:Animals; D004435:Eating / Q000187:drug effects; D020738:Leptin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D015656:Respiratory Mechanics / Q000187:drug effects*; D013990:Tidal Volume / Q000187:drug effects
chemical_list: D020738:Leptin
keywords: breathing; central chemoreception; leptin; obesity; ventrolateral medulla