Role of leptin and orexin on control of breathing

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570533
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Asahikawa Medical College
• Principal Investigator: NAKANO Hitoshi Asahikawa Medical College, 1^<st> dep.of internal medicine, Instructor, 医学部, 助手 (40221452)
• Project Period (FY): 2002 – 2004
• Keywords: obesity / leptin / orexin / control of breathing / sleep apnea syndrome / obesity hypoventilation

Research Abstract

Leptin, synthesized in adipose tissue, suppresses food intake and increases sympathetic activity. On the other hand, orexin, produced mainly in lateral hypothalamus, stimulates food intake and may maintain arousal state. Although besides appetites both leptin and orexin are associated with the regulation of cardiovascular and autonomic function, roles of these peptides on control of breathing and metabolism remain unclear. Thus, we investigated the central action of leptin and orexin on resting ventilation, hypercapnic ventilatory response (HCVR) and metabolism in Zucker rats. The effects of leptin and orexin were tested in obese Zucker rat as a model of genetic obesity and its lean counterpart as a model of normal growth. A micro-polyethylene catheter was inserted into the lateral cerebroventricle several days before experimental date. Animals were anesthetized with intraperitoneal injection of urethane allowing to breath spontaneously. Ventilation (V_E) was measured by the barometric technique of plethysmography and VO_2 was calculated from inflow-outflow O_2 difference. After resting ventilation for 60 min, 9%CO_2 gas was challenged for 2 min (HCVR). Then after, either 10μg of orexin-A or 10μg of leptin was injected i.c.v. followed by the same protocol as above described was performed. The administration of leptin significantly increased V_T and V_E in lean rats, but not in obese rats. V_E/VO_2 and HCVR were unaffected by leptin in both groups. In lean rats, the administration of orexin significantly increased V_E, VO_2, resulting significant elevation in V_E/VO_2. Furthermore, orexin significantly augmented HCVR. We, therefore, conclude that leptin increases metabolic rate leading to a rise in ventilation under condition with a normal leptin receptor. On the other hand, orexin may stimulate resting ventilation and modulate central chemosensitivity directly via respiratory center.