RESUMO
Background and Objectives: The commissural nucleus of the tractus solitarius (cNTS) not only responds to glucose levels directly, but also receives afferent signals from the liver, and from the carotid chemoreceptors (CChR). In addition, leptin, through its receptors in the cNTS, regulates food intake, body weight, blood glucose levels, and brain glucose retention (BGR). These leptin effects on cNTS are thought to be mediated through the sympathetic-adrenal system. How these different sources of information converging in the NTS regulate blood glucose levels and brain glucose retention remains largely unknown. The goal of the present study was to determine whether the local administration of leptin in cNTS alone, or after local anoxic stimulation using sodium cyanide (NaCN) in the carotid sinus, modifies the expression of leptin Ob-Rb and of c-Fos mRNA. We also investigated how leptin, alone, or in combination with carotid sinus stimulation, affected brain glucose retention. Materials and Methods: The experiments were carried out in anesthetized male Wistar rats artificially ventilated to maintain homeostatic values for pO2, pCO2, and pH. We had four groups: (a) experimental 1, leptin infusion in cNTS and NaCN in the isolated carotid sinus (ICS; n = 10); (b) experimental 2, leptin infusion in cNTS and saline in the ICS (n = 10); (c) control 1, artificial cerebrospinal fluid (aCSF) in cNTS and NaCN in the ICS (n = 10); (d) control 2, aCSF in cNTS and saline in the ICS (n = 10). Results: Leptin in cNTS, preceded by NaCN in the ICS increased BGR and leptin Ob-Rb mRNA receptor expression, with no significant increases in c-Fos mRNA in the NTSc. Conclusions: Leptin in the cNTS enhances brain glucose retention induced by an anoxic stimulus in the carotid chemoreceptors, through an increase in Ob-Rb receptors, without persistent changes in neuronal activation.
Assuntos
Corpo Carotídeo , Leptina , Receptores para Leptina , Núcleo Solitário , Animais , Glicemia/metabolismo , Corpo Carotídeo/metabolismo , Glucose/metabolismo , Hipóxia , Leptina/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores para Leptina/metabolismo , Núcleo Solitário/metabolismoRESUMO
Leptin is a protein hormone that plays a key role in the regulation of energy balance and glucose homeostasis. Leptin and all leptin receptor isoforms are present in the carotid bodies, but its precise function in glucose regulation and metabolism is not yet known. The aim of this study was to determine whether exogenous leptin, microinjected into the commissural nucleus tractus solitarii (cNTS), preceding sodium cyanide (NaCN) injection into the circulatory isolated carotid sinus (ICS), in vivo, modifies hyperglycemic reflex (HR) and brain glucose retention (BGR). In anesthetized Wistar rats (sodium pentobarbital, i.p. 3.3 mg/100 g/saline, Pfizer, Mex), arterial and venous blood samples were collected from silastic catheters implanted in the abdominal aorta and jugular sinus. Exogenous leptin (50 ng/20 nL of aCSF) or leptin vehicle (20 nL of aCSF) microinjected (stereotaxically) into the cNTS 4 min before NaCN (5 µg/100 g/50 µL saline into ICS) (experimental 1 [E1] and control 1[C1] groups, respectively) significantly increased HR and BGR compared with their basal values, but the increase was bigger in the E1 group. When leptin or aCSF were injected into the cNTS before saline (E2 and C2 groups, respectively) glucose responses did not vary when compared with their basal levels. Leptin and its receptors in the cNTS cells probably contribute to their sensitization during hypoxia.