Role of leptin and insulin on renal sympathetic nerve activity in high fat fed rabbits

Abstract

We determined the rapidity of changes in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in response to a high fat diet using conscious rabbits and whether this involved insulin and leptin actions in the CNS. New Zealand White rabbits were implanted with renal electrode to measure RSNA. Rabbits were then placed on a normal or 13.5% high fat diet (HFD) for 1 or 3 weeks. Reflexes and stress responses were examined weekly. Rabbits were infused with peptide antagonists of Leptin (100μg) and Insulin (0.5U) intracerebroventricularly at week 1 and 3. After 1 week on the HFD, rabbits demonstrated a 4%, 8% and 30% greater BP, HR and RSNA, respectively (P<0.05). By the end of 3 weeks of HFD, BP, HR and RSNA were elevated by 10%, 5% and 82% (n=9). The insulin antagonist was most effective at 1 week in lowering BP, HR and RSNA while the leptin antagonist was most effective at 3 week of a HFD. The antagonists were minimally effective in control rabbits at these times. Sympathetic activation occurs rapidly within several days of a high fat diet initially associated with forebrain insulin signalling and later as fat is deposited, with forebrain leptin signalling. These changes appear to be associated with pathways mediating the sympathetic responses to acute emotional stress that are independent of baroreflex or chemoreflex pathways.