407 THE CONTRIBUTION OF LEPTIN AND INSULIN TO THE ACTIVATION OF SYMPATHETIC NERVOUS SYSTEM DURING HIGH FAT DIET

Abstract

Objective: We determined the contribution of insulin and leptin signalling in the CNS to the increase in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) following a initiation of a high fat diet (HFD). Methods: New Zealand rabbits were implanted with an intracerebroventricular (ICV) catheter and a renal sympathetic nerve activity (RSNA) electrode and placed on a normal or a high fat diet for 1 or 3weeks. At week 1 and 3 of diet, rabbits were administered a leptin antagonist (100 μg), insulin antagonist (0.5U) or Ringer's. Plasma glucose and insulin levels were determined weekly. Results: Rabbits had higher BP, HR, RSNA, plasma insulin and leptin at 1 and 3 weeks of a HFD compared to controls (n = 6–8). ICV Insulin antagonist reduced BP and HR but not RSNA at week 1 and week 3 of a HFD (P < 0.05). There was no effect of leptin antagonist on BP, HR and RSNA at 1 week HFD, but at 3 weeks the leptin antagonist produced a marked hypotension and reduction in RSNA(P < 0.0001). The leptin and insulin antagonist doses were confirmed in separate animals to effectively block the pressor responses to ICV leptin and insulin respectively. Conclusion: Leptin plays a key role in the CNS contributing to the pressor and tachycardic effects as well as renal sympathetic nerve activity in the pathophysiology of obesity. Insulin has no effect on renal sympathetic nerve activity but actively controls MAP and HR in the early stages of obesity